Neurology India

Print ISSN 0028-3886

E-ISSN 1998-4022

The Official Journal of the Neurological Society of India

Editorial Board
Editor in Chief
P Sarat Chandra
Editorial Assistants
Saumya Awasthi Prakamya Gupta
Co-Editors
AB Taly Manjari Tripathi Arivazhagan BRM Rao
Deepak Agarwal Geeta Chacko Girish Menon Jyotirmoy Banerjee
MC Sharma Mathew Abraham YR Yadav
Assistant Editors
Aparna Dixit Jitin Bajaj Ramesh Doddamani
Deepa Dash Rajesh Kumar Singh
Rajesh Kumar Meena Bhawna Sharma
Bhargavi Ramanujam Kanwaljeet Garg
Advisory Panel
Atul Goel A Nalini B Indira Devi BK Misra
BS Sharma Daljit Singh M V Padma Parampreet Kharbanda
Sangeeta Ravat Suresh Nair Suresh Sankhla Urvashi Shah
VG Ramesh Vivek Lal
Video Editors
Chinmaya Dash Manmohan Singh Roopesh Kumar Satish Verma
(Section-in-charge) Vivek Tandon
Shibu Pillai
Members
Ashish Bindra Girija Rath M Kiran Nishant Goyal
Rabi Sahu Rajesh Chhabra Sachin Borkar Samhita Panda
Shabari Girishan Sheffali Gulati Sanjib Sinha Sumit Bansal
KP Vinayan
Ombudsman
Prof PN Tandon Prof P Satish Chandra Prof Sarla Das
Past Editors
1952-57: B. Ramamurthi 1958-64: R. G. Ginde 1965-78: Anil P. Desai 1979-82: P. N Tandon
1983-84: Asoke K. Bagchi 1985-90: S. Kalyanaraman 1991-96: J.S. Chopra 1997-02: S. Prabhakar
2003-08: Atul Goel 2009-14: JMK Murthy 2015-19: Sanjay Behari

Neurological Society of India

(Executive Committee 2018-19)
President: Lokendra Singh
Honorary Secretary: N. Muthukumar
Honorary Treasurer: Daljit Singh
Editor, Neurology India: P Sarat Chandra
Past Presidents
Deepu Banerji Ramesh C. Mishra Suresh Nair

Executive Committee Members

Achal K. Srivastava Dilip Panikar Girish Menon
J.K.B.C. Parthiban K. Sridhar Lakshmi Narasimhan
Manjari Tripathi Rakesh Jalali Sanjay Pandey
Y. R. Yadav

Neurology India | Volume 69 | Supplement 2 | November-December 2021 Si

Neurology India
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Neurology India Free full text at
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November-December, 2021 CONTENTS Volume 69, Supplement 2

Editor’s Foreword
Hydrocephalus: An Odyssey of Trials, Tribulations, and Eternal Hope Tamaso
Ma Jyotirgamaya (“Lead me from Darkness to Light”)
Sarat P Chandra S257

SECTION I - INTRODUCTION AND BASIC SCIENCE

Hydrocephalus: A Historical Perspective Down the Memory Lane
Prakash N Tandon S259

Hydrocephalus Research
Ashok K. Mahapatra S264

Genetics and Molecular Pathogenesis of Human Hydrocephalus

Maria Garcia‑Bonilla, James P McAllister, David D Limbrick Jr S268

Mathematical Modelling in Hydrocephalus

Agnieszka Kazimierska, Arkadiusz Ziółkowski, Magdalena Kasprowicz, Afroditi Lalou,
Zofia Czosnyka, Marek Czosnyka S275

Hydrocephalus in Children: A Neuroradiological Perspective

Charles Raybaud, Pradeep Krishnan S283

Hydrocephalus in Low and Middle‑Income Countries ‑ Progress and Challenges

Johannes M N Enslin, Nqobile S Thango, Anthony Figaji, Graham A Fieggen S292

SECTION II - FETAL, NEONATAL AND PAEDIATRIC HYDROCEPHALUS

Fetal Ventriculomegaly and Hydrocephalus – What Shouldn’t be Missed
on Imaging?
Liat Ben Sira, Danil A. Kozyrev, Dafna Ben Bashat, Shlomi Constantini, Jonathan Roth,
Shelly I. Shiran S298

Prenatal Ventriculomegaly – Diagnosis, Prognostication and Management

Vivek Krishnan, Akshatha Sharma, Rachita Ramamurthy, Rinshi Elayedatt,
B S Ramamurthy S305

Management of Posthemorrhagic Hydrocephalus

Naren Nayak, Suresh K Sankhla S313

Post‑Infective Hydrocephalus
Kanwaljeet Garg, Deepak Gupta S320

Hydrocephalus in Tuberculous Meningitis ‑ Pearls and Nuances

Vimal K Paliwal, Ravindra K Garg S330

Diagnostic Nuances and Surgical Management of Arrested Hydrocephalus

Manas K Panigrahi, Sandhya Kodali, Y B V K Chandrsekhar, Sudhindra Vooturi S336

Neurology India | Volume 69 | Supplement 2 | November-December 2021 Siii

Neurology India Free full text at
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November-December, 2021 CONTENTS Volume 69, Supplement 2

Hydrocephalus Associated with Posterior Fossa Tumors: How to

Manage Effectively?
Natarajan Muthukumar S342

Management of Complex Hydrocephalus

Abhirama Chandra Gabbita, Subodh Raju S350

Evaluation and Management of Patients with Hydrocephalus in

Craniosynostosis
Jaime Grant, Jagajeevan Jagadeesan, Pasquale Gallo, Desiderio Rodrigues S357

Chiari 1 and Hydrocephalus – A Review

Himanshu Sharma, Jeffrey M Treiber, David F Bauer S362

Hydrocephalus in Spina Bifida

Jeffrey P Blount, Pedram Maleknia, Betsy D Hopson, Brandon G Rocque,
W Jerry Oakes S367

Neurofibromatosis Type 1 Related Hydrocephalus

Jonathan Roth, Shlomi Constantini S372

Hydrocephalus in Vein of Galen Malformations

Srinivasan Paramasivam S376

Applications of Machine Learning in Pediatric

Hydrocephalus: A Systematic Review
Bhavya Pahwa, Ojasvini Bali, Sarvesh Goyal, Shweta Kedia S380

Pediatric to Adult Hydrocephalus: A Smooth Transition

Manilyn A. Hong, Arvind Sukumaran, Jay Riva-Cambrin S390

SECTION III - ADULT HYDROCEPHALUS

A Comparison of Adult and Pediatric Hydrocephalus
Chandrashekhar Deopujari, Chandan Mohanty, Harshal Agrawal, Sonal Jain,
Pawan Chawla S395

Normal‑Pressure Hydrocephalus ‑ Patient Evaluation and Decision‑Making

Deepti Vibha, Manjari Tripathi S406

Comparison of Programmable and Non‑Programmable Shunts for Normal

Pressure Hydrocephalus: A Meta‑Analysis and Trial Sequential Analysis
Varidh Katiyar, Ravi Sharma, Vivek Tandon, Kanwaljeet Garg, Priya Narwal,
P Sarat Chandra, Ashish Suri, Shashank S Kale S413

Post Traumatic Hydrocephalus: Incidence, Pathophysiology and Outcomes

Phelix Rufus, Ranjith K. Moorthy, Mathew Joseph, Vedantam Rajshekhar S420

Subarachnoid Hemorrhage and Hydrocephalus

Suchanda Bhattacharjee, Das Rakesh, Reddy Ramnadha, Panigrahi Manas S429

Idiopathic Intracranial Hypertension ‑ Challenges and Pearls

Wadikhaye Rohit, Alugolu Rajesh, Rukmini Mridula, Shaik A Jabeen S434

Siv Neurology India | Volume 69 | Supplement 2 | November-December 2021

Neurology India Free full text at
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November-December, 2021 CONTENTS Volume 69, Supplement 2

Malignant Meningitis Associated with Hydrocephalus

Ashutosh Kumar, Jayesh C Sardhara, Guramritpal Singh, Soumen Kanjilal,
Ved P Maurya, Sanjay Behari S443

Spontaneous Intracranial Hypotension ‑ A Dilemma

Dhaval Shukla, Nishanth Sadashiva, Jitender Saini, Sriganesh Kamath S456

SECTION IV - SURGICAL MANAGEMENT AND COMPLICATIONS

Shunt Implants – Past, Present and Future
Dwarakanath Srinivas, Gaurav Tyagi, Gyani J Singh S463

Techniques and Nuances in Ventriculoperitoneal Shunt Surgery

Shibu V Pillai S471

A Brief Review of Ventriculoatrial and Ventriculopleural Shunts

Thirumal Yerragunta, Vijaya Sekhar Manda, Vamshi Krishna Yerramneni,
Ram Nath Reddy Kanala  S476

Lumboperitoneal Shunts ‑ Patient Selection, Technique, and Complication

Avoidance: An Experience of 426 Cases
Mallika Sinha, Jitin Bajaj, Ambuj Kumar, Ketan Hedaoo, Sandeep Sharma,
Kamesh Konchada, Shailendra Ratre, Vijay S Parihar, Narayan M Swamy, Yad R Yadav S481

The Leftover Shunts ‑ Ventriculosubgaleal, and Ventriculocholecystal Shunts

Sandip Chatterjee S488

Shunt Complications – Staying Out of Trouble

Chidambaram Balasubramaniam S495

Endoscopic Third Ventriculostomy ‑ A Review

Yad Ram Yadav, Jitin Bajaj, Shailendra Ratre, Nishtha Yadav, Vijay Parihar,
Narayan Swamy, Ambuj Kumar, Ketan Hedaoo, Mallika Sinha S502

Endoscopic Third Ventriculostomy and Choroid Plexus Coagulation in

Infants: Current Concepts and Illustrative Cases
Ronnie E Baticulon, Michael C Dewan S514

Complications Encountered with ETV in Infants with Congenital Hydrocephalus

Rajat Verma, Chhitij Srivastava, Bal Krishna Ojha, Anil Chandra, R K Garg,
Monica Kohli, Hardeep Singh Malhotra, Anit Parihar, Shalini Tripathi S520

Indian Society of Pediatric Neurosurgery Consensus Guidelines on Preventing

and Managing Shunt Infection: Version 2020‑21
Suhas Udayakumaran, Shibu Pillai, Srinivas Dwarakanath, Suchanda Bhattacharjee,
Naveen Mehrotra, Subodh Raju, Deepak Gupta, Manas Panigrahi,
Neelam K Venkataramana, Vedantam Rajshekhar, Suresh Sankhla S526

Neurology India | Volume 69 | Supplement 2 | November-December 2021 Sv

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November-December, 2021 CONTENTS Volume 69, Supplement 2

SECTION V - OUTCOMES AND CONTROVERSIES IN HYDROCEPHALUS

Clinical Outcome, Cognitive Function, and Quality of Life after Endoscopic
Third Ventriculostomy versus Ventriculo‑Peritoneal Shunt in
Non‑Tumor Hydrocephalus
Manju Dhandapani, Nishant S. Yagnick, Manju Mohanty, Chirag K. Ahuja,
Sivashanmugam Dhandapani S556

Natural History, Treatment Outcomes and Quality of Life in Idiopathic

Normal Pressure Hydrocephalus (iNPH)
Albert M Isaacs, Mark Hamilton S561

Three Decades of Vellore Grading for Tuberculous Meningitis with

Hydrocephalus: A Reappraisal
Vedantam Rajshekhar S569

Controversies in Hydrocephalus: QUO VADIS

Suhas Udayakumaran, Jogi V Pattisapu S575

NI Feature: The First Impression

The First Impression
Mahendra Singh Chouhan S583

Svi Neurology India | Volume 69 | Supplement 2 | November-December 2021

 Editor’s Foreword
Access this article online
Quick Response Code:
Website:
www.neurologyindia.com
DOI:
10.4103/0028-3886.332250
Department of
Neurosurgery, All India
Institute of Medical
Sciences (AIIMS),
Delhi, India
Address for
correspondence:
Dr. Sarat P Chandra,
Department of
Neurosurgery, All India
Institute of Medical
Sciences (AIIMS),
Delhi‑ 110 029, India
E‑mail: saratpchandra2@
gmail.com
© 2021 Neurology India, Neurological Society of India | Published by Wolters Kluwer - Medknow S257
Hydrocephalus: An Odyssey of Trials,
Tribulations, and Eternal Hope Tamaso
Ma Jyotirgamaya (“Lead me from
Darkness to Light”)
Sarat P Chandra
   Jogi V. Pattisapu Suchanda Bhattacharjee Suhas Udayakumaran Sarat P Chandra
Hydrocephalus is the most widely
managed condition in neurosurgery, and its
pathophysiology has intrigued neuroscientists
for over a century. Neurology India is pleased
to bring together a collection of articles
encompassing varied topics ranging from
benchwork to clinical science to improve the care
of the hydrocephalic patient.
Friends, this Neurology India supplement is
our humble effort to bring leading thinkers
in this field from around the globe to share
their knowledge and understanding. We are
incredibly grateful to the many authors and
reviewers, and this worldwide effort has shown
us yet another shining example of the spirit of
service, sharing, and education.
This extensive and perhaps incomplete collection
of articles submitted by all strata of thinkers from
the youngest to the most senior and from bench
to clinics brings together exemplary quality and
content to benefit our readership. Debates and
discussions are always happening regarding
hydrocephalus, mainly since many details are
not very well understood. Therefore, we tried
to be inclusive by bringing different opinions
and options for our readers in this publication.
This is an open access journal, and articles are distributed under the terms
of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0
License, which allows others to remix, tweak, and build upon the work
non‑commercially, as long as appropriate credit is given and the new
creations are licensed under the identical terms.
For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com
The supplement is divided into five thematic
schemes with relevant subtopics to cover all
facets of hydrocephalus. Although most aspects
of the condition were included, we realize
that some could not be reviewed in detail. The
team humbly requests your understanding and
forgiveness for any errors or omissions in this
regard.
We are grateful to the Neurology India team,
especially Mrs. Saumya Awasthi and the
Editor‑in‑Chief, Prof. Sarat Chandra of AIIMS.
The team is hopeful that this work will serve as
a spark for further research and benefit all those
afflicted by hydrocephalus. In that spirit, we
dedicate this supplement to our patients who
patiently hope, waiting for improvements with
simple trust.
Foreword by the Editor – in Chief,
Neurology India
A ventriculoperitoneal shunt may be one of the
first surgeries performed by a neurosurgery
resident. While this is often straightforward to
perform, I would consider this among the most
challenging surgery. This, of course, is realized
How to cite this article: Chandra SP. Hydrocephalus:
An Odyssey of Trials, Tribulations, and Eternal Hope
Tamaso Ma Jyotirgamaya (“Lead me from Darkness
to Light”). Neurol India 2021;69:S257-8.
Submitted: 02‑Nov‑2021   Revised: 02‑Nov‑2021
Accepted: 17‑Nov‑2021   Published: 11-Dec-2021
 Editor’s Foreword
by the neurosurgeon only as time passes by and as they gain
experience. Every complication has been described for a shunt
surgery for hydrocephalus, starting with shunt malfunction,
infection, and even shunt‑related hematomas. Hydrocephalus
still happens to be among the most challenging pathologies
to deal with. The burden on caregivers is tremendous. The
family goes through a lot, enduring the tribulations of a near
and dear one who has undergone a shunt for hydrocephalus.
Every time the patient has a fever, the whole family is
stressed out, whether it is a shunt infection. Every time the
patient complains of headache, there is a lot of duress and
apprehension, whether it is a shunt malfunction. The surgeon
often is outfoxed because of multiple shunt revisions or
development of ascites, again making the surgeon think of
other procedures like a ventriculoatrial or ventriculo‑pleural
shunt. Though it has opened a new window for hydrocephalus,
endoscopic third ventriculostomy is still not without risks and
dangers. Performing an endoscopic third ventriculostomy for
a beginner and working so close to vital structures like the
hypothalamus and basilar artery may not be a comfortable
feeling. Treatment of hydrocephalus does not respect the
“seniority and experience of the neurosurgeon.” Even the
most experienced neurosurgeons would have had cases that
would have tested their skills to the limit.
The literature has approached this pathology with a certain
degree of disdain. Most neurosurgeons are more comfortable
S258 Neurology India | Volume 69 | Supplement 2 | November-December 2021
dealing with other pathologies like skull base, epilepsy
surgery, functional, or cerebrovascular. So much has been
the frustration in dealing with this pathology that most
neurosurgeons think that nothing better may be achieved
for this.
For the same reason, a supplement on hydrocephalus has
been long since due. I could not have asked a better author
to take charge of this supplement. Prof Jogi Pattisapu, with
his team, Ad. Prof Suchanda Bhattacharjee and Prof Suhas
Udayakumaran, has done an exemplary job in compiling this
difficult supplement. They have been patiently contacting
all the authors and diligently proofreading every article to
ensure no mistakes. Neurology India is truly indebted to
them.
I hope that this supplement will become a reference material
for residents and younger faculty and for senior neurosurgeons
in strengthening their knowledge of hydrocephalus. I would
consider this supplement as a monogram for hydrocephalus
and would become more like a reference textbook.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
 Historical Perspective

Access this article online

Quick Response Code:
Hydrocephalus: A Historical
Perspective Down the Memory Lane
Prakash N Tandon

Website: Abstract:
www.neurologyindia.com
This is a personal account of evolution of knowledge about the etio-pathogenesis, diagnosis and treatment of
DOI: over three decades as a student and later a professional neurosurgeon. This reflects an historical perspective
10.4103/0028-3886.332244 on the subject not withstanding the tremendous advances that have taken place in the field. It is regrettable
that a successful management of hydrocephalus leave aside its cure, still eludes us.
Key Words:
Hydrocephalus, communicative, obstructed, normal pressure, congenital, post-inflammatory, CSF diversion

Key Message:
A multidisciplinary approach, not only of neurobiologists, but of basic scientists, mathematicians, physicians
along with specialist in hydrodynamics and technologists is urgently required to improve the management
and if, possible cure of this disorder.

A child’s swollen head, bulging fontanelle,

and separated sutures are so obvious that
these could not have been missed the attention
of Sushruta, Charak, Hippocrates, or Celsus. It
is claimed that Vesalius (1514–1564) gave a clear
account of internal hydrocephalus. However,
no history of the condition was available to the
author before 1790.[1] According to our medical
historian Sunil Pandya, the earliest description
appeared in the first issue of Lancet in 1823
by Barnard. [2] Charles Morehead (1847‑48)
from Bombay (now Mumbai) described post
meningitic hydrocephalus in children, and
50 years later, Ferguson reported intraperitoneal
diversion of cerebrospinal fluid (CSF) for
hydrocephalus.[3,4]
Cushing, while operating on an intraventricular
tumor, first observed CSF be secreted by the
choroid plexus. However, Dandy unequivocally
established this fact based on experimental
Department of studies and further demonstrated CSF flow
Neurosurgery, AIIMS, through the ventricular system into the
National Brain subarachnoid space for absorption.[5,6] He later
Research Institute, described the cause of idiopathic hydrocephalus
Manesar, Haryana, and attempted to treat the condition by excision
India of the choroid plexus (with limited success).[5]
Remarkably, the renowned British anatomist
Address for
Thomas Willis (1621–1675) had earlier claimed
correspondence:
Dr. Prakash N Tandon, that choroid plexuses are the site of CSF
Department of
Neurosurgery, AIIMS This is an open access journal, and articles are distributed under the terms
and National Brain of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0
Research Centre, License, which allows others to remix, tweak, and build upon the work
Manesar ‑ 122 051, non‑commercially, as long as appropriate credit is given and the new
creations are licensed under the identical terms.
Haryana, India.
E‑mail: tandon@nbrc.ac.in For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com
formation. Mullener’s (1965) [7] details of
early history can be found in Sach’s “The
History and Development of Neurological
Surgery,”[8] in Milhorat’s, “Hydrocephalus and
Cerebro‑Spinal Fluid,”[9] and more recently, in
our “Textbook of Neurosurgery” by Tandon and
Ramamurthi (2012).[1]
Pathology
Dorothy Russell [10] from Queens’s Square
London provided the first detailed report on
the pathology of hydrocephalus as a special
report on behalf of the Medical Research Council
in 1949 and revisited the concept in 1968.
Gopinath et al.[11] (1979) and colleagues from
AIIMS described the ultrastructural observations
in experimental hydrocephalus. Shankar[12] (1983)
described the ultrastructure of arachnoid villi in
the human optic nerve, which added to the earlier
description by Jacob Abraham (1973) detailing
the ultrastructure of infant choroid plexus in
hydrocephalus.[13] Following the description by
Luschka and Magendie of the outlet foramina
of the 4th ventricle, Dandy and Blackfan[14] (1913)
described the now well‑known syndrome of
pan‑ventricular obstructive hydrocephalus.
Taggart and Walker (1942),[15] Fisher (1973),[16]
and Raimondi (1984) [17,18] further elaborated
this syndrome. Pandya et al. (1974)[19] described
How to cite this article: Tandon PN. Hydrocephalus:
A Historical Perspective Down the Memory Lane.
Neurol India 2021;69:S259-63.
Submitted: 22‑Sep‑2021 Revised: 05-Oct-2021
Accepted: 09-Oct-2021 Published: 11-Dec-2021

© 2021 Neurology India, Neurological Society of India | Published by Wolters Kluwer - Medknow S259
 Tandon: Hydrocephalus: Down the memory lane
this condition from the Indian subcontinent. Dastur and
Lalitha (1973),[20] Dastur, Pandya and Rao (1972),[21] Tandon and
Pathak (1978)[22] provided a detailed account of the pathology
of tuberculous meningitis and associated hydrocephalus.
Investigations
Dandy was the first to visualize the ventricular system utilizing
air ventriculography and pneumoencephalography, which
remained the most important, really the only, investigation to
confirm the diagnosis.[5] Using these investigations, difficulties
related to a clear visualization of the aqueduct and the fourth
ventricle led to positive contrast ventriculography.[23‑28]
Around the same time, two noninvasive techniques were
developed to assess the ventricular size, that is, A‑scan
echoencephalography[29] and isotope cisternography (I131
RIHSA), which provided a more comprehensive view of the
CSF pathways and circulation.[30‑33] The development of CT and
MRI overshadowed all these techniques.[34]
Treatment
Until the mid‑20 th century, treatment of communicating
hydrocephalus had been a consistent failure. Compression of
the head,[35‑37] oral acetazolamide (Diamox),[38‑45] glycerol,[46,47]
or isosorbide was utilized without success.[39‑45] Similarly,
others tried ouabain, furosemide, and steroids as prophylactic
treatments, with no consistent success, and undoubtably, there
were occasional cases of arrested hydrocephalus.
Following Dandy’s[5] example (1918), ingenious operations
were attempted for obstructive hydrocephalus. Techniques
were developed to destroy the choroid plexus in the lateral
ventricles by cauterization,[48] and attempts were made to do
an IIIrd ventriculostomy for communicating hydrocephalus,
obviously not realizing its pathophysiology.[49‑52]
In contrast, Torkildsen (1939) from Norway devised a palliative
operation for cases of obstructive hydrocephalus, that is,
ventriculocisternostomy to connect the lateral ventricle to
cisterna magna.[53,54] Similarly, Elvidge[55] (1966) from Montreal
reported the treatment of aqueductal atresia by cannulating
it—an operation called interventriculostomy. Subsequently,
Backlund et al.[56] (1981) described the stereotaxic reconstruction
of the aqueduct.
Dandy[57] (1921) described third anterior ventriculostomy
for treatment of aqueductal atresia. Two years later, Mixter
reported using an endoscope [58] for the operation, and
Scarff (1935) modified the technique by using improved
instruments.[58] However, with the availability of unidirectional
shunts, the operation was infrequently used until Bracklehurst
revived it in 1974.[59] However, the operation gained popularity
recently with the advent of endoscopic surgery,[50,60,61] and Kelly
et al.[62] (1986) added CT‑guided stereotaxy for this purpose.
As early as 1898, Ferguson described CSF diversion to
the peritoneal cavity.[4] Nulsen and Spitz  (1952)  reported
a direct ventricle to jugular vein shunt.[63] Subsequently,
Pudenz  et al. [64] (1957) recommended the diversion of
ventricular fluid into the right atrium. It may be mentioned
S260 Neurology India | Volume 69 | Supplement 2 | November-December 2021
this was prior to the development of unidirectional flow shunt
valves. However, the following year, Pudenz et al.[64] (1957)
reported his well‑known ventriculoatrial (VA) shunt using
a valve for unidirectional regulated flow of CSF. He further
reported his experience in 1966.[65] The Spitz–Holter shunt
soon followed this[63] and revolutionized the treatment of both
communicating and obstructive hydrocephalus.
In the meantime and even for some years following, various
operations were devised to divert the ventricular CSF to a
cavity where it could be absorbed. This included operations
such as ventriculopleural shunt, [66] ventricle to Stenson’s
duct (Parkinson and Jain, 1961),[67] peritoneal shunt using
fimbria of the fallopian tube by Harsh in 1954,[68] ventricle
to ureter[69] (Matson, 1969), among others. Over the years, a
variety of shunt operations were developed, but the most
common today is the ventriculoperitoneal shunt (VP) using a
standardized shunt assembly (with various characteristics to
suit an individual patient’s needs). Several large series have
reported the outcome of these operations.[9,35,49,70]
However, it must be mentioned that an ideal operation for
the treatment of hydrocephalus has not yet been devised.
The current shunt operations are beleaguered by more
complications than any other neurosurgical operation. (The
literature is full of such reports, and I am sure they will be
elaborated in other articles).
Another entity requiring brief mention is the so‑called “normal
pressure hydrocephalus,” first described by Adams et al. from
Boston in 1965.[71] This is characterized by gait abnormality,
progressive dementia, and dilated ventricles without
symptoms of raised intracranial pressure. This was further
elaborated by Hakim and Adams (1965),[71,72] Black (1980),[73]
and Miller Fisher (1977).[74] The pathogenesis has been a subject
of some interest and debate, and the symptoms are relieved by
VA or VP shunt if the diagnosis is correct.
Some Personal Anecdotes and Indian Experience
My first encounter with a patient with univentricular
hydrocephalus due to an intraventricular tumor was also
my initial exposure to neurosurgery in Oslo, Norway, under
Prof. Kristian Kristiansen. Removal of an intraventricular
epidermoid relieved the patient of her hydrocephalus raised
intracranial pressure and long‑standing focal epilepsy (Tandon
1958).[75] Soon after, I encountered a patient with a brain
stem tumor with obstructive hydrocephalus, who one day
was suddenly relieved of his signs and symptoms of raised
intracranial pressure. Some months later, he was readmitted
with generalized seizures and expired. An autopsy revealed
a spontaneous ventriculocisternostomy that relieved
his hydrocephalus (Tandon and Harkmark, 1959). [76] I
participated in a Torkildsen’s operation performed by Prof.
Kristiansen (who was earlier trained by Torkildsen) on a
young girl for aqueductal atresia. I had the privilege to meet
Torkildsen, who was now in private practice. However, during
my two years in Oslo, no unidirectional shunt was performed
as it was not available. I saw this performed for the first time
at Montreal Neurological Institute (MNI). As a matter of
fact, Pudenz, who devised this shunt, had his neurosurgical
training there.
 Tandon: Hydrocephalus: Down the memory lane
A lesson we learned early on should serve as a guiding light.
A young girl 10–12 years old with hydrocephalus went through
21 revisions of shunt operations during nearly 3 months of
hospitalization. Though we lost hope and were willing to give
up, she and her mother encouraged us to try again and again.
She ultimately recovered fully, grew up normally, married, had
children, and I am informed that she is leading an everyday life.
On coming to India, these recently developed shunts were not
available. I tried ventriculoperitoneal shunts using Ryle’s tube,
which at best provided relief for a few days but generally proved
to be a failure. We finally managed to get some of these shunts
while at AIIMS, but these were rather costly. Help came when
my old school‑mate, Prof. Purushottam Upadhyaya, Chief of
Pediatric Surgery, developed such a shunt in his departmental
laboratory and provided it to us virtually for free.[77,78] By now,
our interest had shifted to evaluate I131 RIHSA‑Cisternography
as a diagnostic and prognostic technique.[31,32]
The cost of imported shunts being generally unaffordable,
two other groups in India indigenously developed these. Thus
came the affordable and reliable Chhabra Shunt (Mittal et al.
1992,[79] Chitra shunt).[80]
An area in which Indian neurosurgeons contributed
significantly was post‑tuberculous meningitic hydrocephalus.
However, let me first mention the pioneering contribution
of an Indian microbiologist who soon after the availability
of streptomycin in the country described its pathogenic role
in developing hydrocephalus in patients of tuberculous
meningitis (De, 1949).[81] Post‑meningitic hydrocephalus being
a prevalent condition in India, it became a subject of several
pioneering studies, for example, Pathology (Dastur and
Lalitha 1973, Dastur and Pandya 1972, Tandon and Pathak
1973, Tandon PN 1978),[1,20‑22] and we became interested in
its pathogenesis in the early 1970s. Our studies on isotope
cisternography in these cases revealed original findings of
pathogenic, pathological, and therapeutic interest; these were
the first such studies and worth quoting.
Isotope scanning of CSF pathways thus revealed abnormalities
of pathways and/or flow dynamics in two‑third of cases of
tuberculous meningitis. It established the precise cause of
raised intracranial pressure and hydrocephalus in all such
patients. The site of obstruction in CSF pathways could be
single or multiple, and this study provided information hitherto
not available to enable evidence‑based rationale.[31,32]
With the availability of CT scans, this investigation could
be replaced. We were the earliest to evaluate the use of CT
for the diagnosis of tuberculous meningitis and associated
hydrocephalus.[34,82]
Over the years, several Indians such as Bhatia and Tandon (1978),
Upadhyaya et al. (1983), Palur et al. (1991), Agrawal, et al. (2005),
Sil and Chatterji (2008), and Srikantha et al. (2009) reported
numerous cases with series of tuberculous meningitis
associated hydrocephalus clinical features, CT findings, and
the result of surgery.[77,83‑87] Bhagwati[88] (1971) reported a series
of patients of post meningitic hydrocephalus treated with a
ventriculoatrial shunt, and a similar series was reported by
Upadhyaya et al. (1983).[77]
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S261
Another area of interest to Indian neurosurgeons was
preoperative use of VP shunt insertion for patients with
hydrocephalus due to large posterior fossa tumors in poor
clinical condition, initiated by Abraham and Chandy (1963),[89]
and several others including us (Lodha et al. 1981)[90] and
Goel (1993).[91]
Conclusion
We reviewed some progress in understanding CSF flow issues
and a few contributions made from the Indian subcontinent
related to hydrocephalus. Notwithstanding recent advances in
brain fluid dynamics and shunt technology, it is disappointing
that the operations to deal with the condition continue
to be associated with many complications. The history of
hydrocephalus is not yet done, and future research efforts will
improve the lives of our patients and their families.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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 Review Article

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Quick Response Code:
Hydrocephalus Research
Ashok K. Mahapatra

Abstract:
Objective: This paper highlights the hydrocephalus research efforts undertaken at AIIMS, New Delhi,
Website: supporting progress in the field.
www.neurologyindia.com
Material: Over a period of three decades, basic research, clinical investigations, and multicentric studies were
DOI: undertaken. This report will review the work mainly to emphasize the need for future generations to pursue
10.4103/0028-3886.332258 further research. Studies that impacted hydrocephalus care (mainly in India) are described, and some of these
findings may be useful in other resource‑challenged situations.
Results: Investigative studies on the effect of shunting on brainstem auditory evoked responses (BAER),
transcranial Doppler  (TCD), and CT‑SPECT were published offering management options for patients.
Participation in the International Infant Hydrocephalus Study (IIHS) study offered opportunities to compare
our approaches and develop modifications in patient care. This effort proved shunting was equal or better
for young children with congenital aqueductal stenosis. Shunt infection protocols and changes made in a
systematic manner helped develop local protocols to reduce postoperative shunt infections.
Conclusions: Hydrocephalus research over three decades at AIIMS, New  Delhi was productive and
educational, confirming that locally performed investigative work can help in decision making. Further studies
and active participation in international efforts are necessary to advance the field.
Key Words:
AIIMS, hydrocephalus research

Key Messages:
Research is crucial to identify issues and enhance care for patients with hydrocephalus. Locally developed
efforts are needed and can be done with diligence, improving specific methods important in resource‑challenged
situations. Further research is needed by future generations, with hopes of positive contributions to improve
outcomes for patients with hydrocephalus.

H ydrocephalus is an increasingly common

neurosurgical problem involving all age
groups with varying etiologies, presentations,
hydrocephalus. Among them, two studies were
investigative, one was a shunt design trial, two
were multinational endeavors, and two on
and treatment outcomes.[1‑10] In the past century, post‑traumatic hydrocephalus. These various
research has advanced our understanding approaches to hydrocephalus research helped
of various aspects of hydrocephalus, us develop strategies and improve outcomes.
including shunt valve design, extent of brain
injury, and the development of endoscopic Observations
procedures.[8‑15] A. In our 1 st  study on brainstem auditory
evoked responses (BAER), 30 patients
Here we highlight our contributions to clinical and with hydrocephalus due to brain tumors
investigative works by the senior author over the w e r e e v a l u a t e d . [15] T h r e e g r o u p s o f
past three decades involving electrophysiology, 10 patients (3rd ventricular tumors, brainstem
Department of
trauma, shunt trials, and cerebral blood flow tumors, and cerebellar tumors) were
Neurosurgery, IMS
dynamics.[15‑21] evaluated pre‑ and post‑operatively with
and SUM Hospital,
BAER studies within 2 days. The study
Bhubaneshwar, Odisha,
Methodology was abnormal in 70% of patients, with
India
all 10 brainstem tumor patients showing
Address for This report gives an overview of the various abnormalities and positive findings in
correspondence: clinical and investigative studies conducted 8/10 cerebellar tumor patients (wave I‑III
Prof. Ashok Kumar to improve evidence‑based management of and III‑V delays). Post‑shunting, 7/10
Mahapatra, Institute brainstem tumor patients had improvement
of Medical Science This is an open access journal, and articles are distributed under the terms
(IMS) and SUM of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 How to cite this article: Mahapatra AK. Hydrocephalus
Hospital, Kalinga Nagar, License, which allows others to remix, tweak, and build upon the work Research. Neurol India 2021;69:S264-7.
Bhubaneswar, Odisha, non‑commercially, as long as appropriate credit is given and the new
creations are licensed under the identical terms. Submitted: 18‑Jun‑2021 Revised: 17‑Aug‑2021
Email: akmahapatra22000@ Accepted: 09‑Oct‑2021 Published: 11-Dec-2021
gmail.com For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com

S264 © 2021 Neurology India, Neurological Society of India | Published by Wolters Kluwer - Medknow
 Mahapatra: Hydrocephalus research

in BAER, but none of the cerebellar tumor patients with Table 1: Findings of Brainstem Auditory Evoked
hydrocephalus showed improvement. In fact, seven of these Responses (BAER) in hydrocephalic patients
patients had surprising deteriorations in BAER after shunt Preoperative Postoperative
insertion (most frequently III‑V delay) [Table 1]. Brainstem tumors All abnormal 70% improved
B. A study based on transcranial Doppler (TCD) findings in 3rd Ventricular tumors 80% None improved
35 patients with hydrocephalus identified both flow velocity Cerebellar tumors 80% 70% deteriorated
and pulsatility indices recovered after shunt insertion.[22‑24] Five patients with III‑V delay
We observed increased flow velocity and high pulsatility
One patient with I‑III delay
index (PI) in 32 patients with moderate hydrocephalus and
One patient with both I‑III and
in three patients with severe (grade III) hydrocephalus. TCD III‑V delays
was done 36–48 hours prior to shunt insertion and was
abnormal in all patients (high PI), with a direct correlation
to ventricle size. Post‑operatively, both flow velocity and Table 2: Transcranial Doppler in Hydrocephalus (TCD)
PI decreased and suggested a good correlation between All 35 patients had abnormal TCD findings
reduction of ventricular size and improvement in cerebral Size of ventricle and abnormalities proportional to each other
blood flow[23] [Table 2]. Pulsatility Index (PI) was abnormal 100%
C. We conducted a prospective study by performing Reduction of ventricle size decreases blood flow velocity and PI
SPECT in patients prior to and following shunt Simple bedside test and clinician friendly
surgery [Table 3A]. Seventeen children under 18 years
were included: 10 with congenital hydrocephalus, five
with associated brain tumors, and two with post‑infection Table 3: Use of SPECT study in hydrocephalus
hydrocephalus. A. Observations B. Post‑op SPECT Findings
We observed a good correlation with clinical improvement 17 patients below 18 years Cerebral perfusion improved in
and increased cerebral perfusion in 12 patients. Symptom 12 patients postoperatively
duration and ventricle size were not significant [Table 3B]. Routine CT Scans Ventricle size reduced in
D. Many authors have analyzed the risk factors for 13 patients
post‑traumatic hydrocephalus (PTH), including occurrence SPECT Pre‑ and 48 hours post‑shuntClinical improvements in all
of epilepsy, herniation, and “Syndrome of Trephine” 10 patients with congenital Duration of symptoms and size
following post‑traumatic hydrocephalus (DC).[25‑27] In our hydrocephalus, five with brain of ventricle not significant.
1st study of 22 patents, none had undergone DC as it was tumors, and two with post meningitis
not routinely practiced at that time.[17] However, in our later
study by Sarkari et al.,[19] all 38 patients had undergone DC, Table 4: Post‑traumatic hydrocephalus (PTH) and
and 65% patients developed hydrocephalus. Improvement hydrocephalus
was reported in 70%–90% patients following shunt insertion A. Oman 1999‑2000 B. AIIMS 2009‑2010
with 18% shunt revision rate[24,25,27] [Table 4].
22 patients 38 patients studied over 24 years; 73%
Moderate and severe head injury patients with patients had a severe head injury
hydrocephalus and prior DC were evaluated, and Severe head injury Subarachnoid hemorrhage 58%
research on PTH yielded first of its kind data in the Indian
Mostly VP Shunt done 65% of patients had decompressive
subcontinent.[16‑19] within 6‑7 weeks craniotomy (DC)
E. We participated in two multicenter shunt studies on
80% had improvement 79% (30) improved after shunt
patients with hydrocephalus. One was designed by
20% did not improve due to Shunt revision was required in 18%
Shree Chitra Thirunal Institution of Medical Science and primary brain injury.
Technology as a 2‑year multicentric study in India with
seven centers, including AIIMS. A total of 120 patients
were enrolled to study a new shunt design; this resulted in equally good options, and the outcomes depend on several
the development of a 3rd shunt system in India (Ceredrain, other parameters.
patented and marketed in India). F. We performed two postoperative neurosurgical infection
The multicentric multinational study IIHS studied shunt studies, with the first study involving 507 cases and
insertion versus endoscopic third ventriculostomy (ETV) the second study enrolling 437  patients. We identified
for treatment of aqueductal stenosis in children aged postoperative shunt infections in 3%–5% of cases,
less than 2 years. A total of 158 patients from 27 centers which decreased over the last 30 years to 2%–3%.[34‑36]
participated in the study with a 5‑year follow‑up.[28‑31] There However, infection rate is still higher in post‑tubercular
was no statistical significance between a shunt and ETV; hydrocephalus.[35‑38]
however, in children below age 6 months, shunt insertion Discussion
had a higher success rate.[28,31]
Our active participation in this trial identified the 3‑month Hydrocephalus is a major health problem, with a significant
success rates as 95% for shunt insertion and 68% for ETV disease burden globally.[1‑8] Among congenital malformations,
with 6‑month success rates being 83% and 66% for the brain abnormalities are most crucial, commanding great
shunt and ETV, respectively.[32,33] At 5‑year quality of life interest over the last century. Since Walter Dandy’s initial
and health utility index analyses, there was no difference attempts until today, much research has been performed on
between the two groups (P = 0.42 and 0.2, respectively). various aspects of hydrocephalus.[5,9‑14] All these studies have
This study helped our global understanding that both are made us visible in the field of pediatric hydrocephalus, clinical,
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S265
 Mahapatra: Hydrocephalus research
and endoscopic trials and basic science research. Such diligent
efforts resulted in the development of a suitable shunt system
and other options to manage this lifelong condition.
This review offers a glimpse of the hydrocephalus research
efforts over the past several decades by the senior author
with support from AIIMS, New Delhi. Several studies helped
enhance our understanding regarding BAER changes related
to hydrocephalus of various causes and the potential for
improvement after interventions.
SPECT and TCD studies helped us understand some anatomical
issues and blood flow changes with this condition and
identify some interesting features of pediatric hydrocephalus.
Tumor‑related and post‑infectious conditions vary in their
response, and more investigations are necessary.
We identified differences related to DC in patients with
post‑traumatic hydrocephalus, and these data helped improve
our management of severely injured patients. Our protocols
and gradual changes in the care of shunted patients helped
reduce the infection rate to international standards. Similarly,
collaborating with other centers nationally and globally
increased our knowledge, while exposing our capabilities.
Together, much has been learned by these efforts, but much
is yet to be done.
For example, the basic pathophysiological basis for poor CSF
circulation or absorption is elusive, demanding a concerted
effort by future researchers. These tough answers will provide
more favorable neuropsychological outcomes for our patients.
Treatment done late is less rewarding as recovery from brain
damage is unpredictable.
Conclusion
Outcome of hydrocephalus treatment is far from optimal
and optimal valve systems for ventricular diversion are yet
to be developed. Controversies exist revolving shunt versus
ETV in infants with hydrocephalus, and selection of patients
for CSF diversion needs to be rationalized in post‑traumatic
hydrocephalus. Our investigative studies have indicated the
need for further research following a method of inexpensive
projects and evidence‑based practice. Over the last 35–40 years,
at AIIMS Delhi, we carried out many studies to find solutions
and described a few studies and some limitations.
We hope our efforts will motivate young academic
neurosurgeons to conduct further studies and enhance our
knowledge in the field of hydrocephalus.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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 Review Article

Access this article online

Quick Response Code:
Genetics and Molecular Pathogenesis
of Human Hydrocephalus
Maria Garcia‑Bonilla, James P McAllister, David D Limbrick Jr

Website: Abstract:
www.neurologyindia.com
Hydrocephalus is a neurological disorder with an incidence of 80–125 per 100,000 live births in the United
DOI: States. The molecular pathogenesis of this multidimensional disorder is complex and has both genetic and
10.4103/0028-3886.332249 environmental influences. This review aims to discuss the genetic and molecular alterations described in human
hydrocephalus, from well‑characterized, heritable forms of hydrocephalus (e.g., X‑linked hydrocephalus from
L1CAM variants) to those affecting cilia motility and other complex pathologies such as neural tube defects and
Dandy–Walker syndrome. Ventricular zone disruption is one key pattern among congenital and acquired forms
of hydrocephalus, with abnormalities in cadherins, which mediate neuroepithelium/ependymal cell junctions
and contribute to the pathogenesis and severity of the disease. Given the relationship between hydrocephalus
pathogenesis and neurodevelopment, future research should elucidate the genetic and molecular mechanisms
that regulate ventricular zone integrity and stem cell biology.
Key Words:
Cell junctions, genetics, hydrocephalus, inflammation, molecular biology, stem cells, ventricular zone disruption

Key Message:
The molecular pathogenesis of hydrocephalus is complex and involves genetic and environmental
factors. Ventricular zone disruption is one key pattern in the different forms of the disease.

H ydrocephalus is the most common disease

treated by pediatric neurosurgeons[1] with
an incidence of 0.3–0.7 per 1,000 live births
in the US. [2] Current treatments are largely
limited to cerebrospinal fluid (CSF) diversion
including CSF shunts or endoscopic third
ventriculostomy with or without choroid plexus
cauterization.[3,4] While nonsurgical treatments
have long been sought, the pathophysiology
of this disorder is complex, involving myriad
genes and environmental factors.[1]
This review focuses on the genetics and molecular
pathogenesis of human hydrocephalus. We
begin by describing the ventricular system
Department of and neuroepithelium/ependyma in normal
Neurosurgery, development before reviewing the genetics
Washington University and molecular biology associated with
in St. Louis School of hydrocephalus. We then describe in detail
Medicine, St. Louis, ventricular/subventricular zone  (VZ/SVZ)
Missouri, USA disruption and dysregulation of cell–cell
junctions as one critically important common
Address for molecular trigger in the pathogenesis of
correspondence: hydrocephalus.
Dr. Maria Garcia‑Bonilla,
Department of
Neurosurgery,
Washington University, This is an open access journal, and articles are distributed under the terms
School of Medicine, of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0
660 S. Euclid. Campus, License, which allows others to remix, tweak, and build upon the work
Box 8057,St. Louis, MO non‑commercially, as long as appropriate credit is given and the new
creations are licensed under the identical terms.
63110, USA.
E-mail: mariag@wustl.edu For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com
The ventricular system, CSF dynamics, and
neuroepithelium/ependyma
According to the bulk‑flow hypothesis, CSF
moves from the two lateral ventricles to the
third ventricle through the foramina of Monro,
and from there to the fourth ventricle through
the aqueduct of Sylvius. CSF exits the fourth
ventricle to the subarachnoid space through
the foramina of Luschka and Magendie, after
which it is reabsorbed into the bloodstream.[5‑7]
Moreover, while beyond the scope of this review,
it is now appreciated that CSF movement is
considerably more complex, with a dynamic
exchange flow between blood, interstitial
fluid, and CSF occurring throughout the entire
brain. [7] The glymphatic system, formed by
perivascular channels and astrocytes, eliminates
soluble protein and metabolites, and distributes
different molecules such as glucose or amino
acids. [8,9] CSF flows from the subarachnoid
space, to the perivascular spaces in the dura,
and from there to the brain parenchyma through
Aquaporin‑4 water channels, mixing with the
interstitial fluid. Parenchymal interstitial fluid
How to cite this article: Garcia-Bonilla M,
McAllister JP, Limbrick DD. Genetics and Molecular
Pathogenesis of Human Hydrocephalus. Neurol India
2021;69:S268-74.
Submitted: 27‑Oct‑2021 Revised: 27-Oct-2021
Accepted: 28-Oct-2021 Published: 11-Dec-2021

S268 © 2021 Neurology India, Neurological Society of India | Published by Wolters Kluwer - Medknow
 Garcia‑Bonilla, et al.: Genetics and molecular pathogenesis of hydrocephalus
flows through perivenous spaces and is collected in the
meningeal and cervical lymph nodes.[8‑12]
At the interface between the brain parenchyma and the
ventricles, the VZ develops as a neuroepithelium, maturing to
a single‑cell, ciliated ependymal layer.[13] During development,
neurogenesis in the neuroepithelium involves radial glial
cells.[14,15] A subpopulation of radial glial cells matures into
nonproliferative ependymal cells, while some radial glia cells
are retained as stem cells, constituting a neurogenic niche in
the SVZ.[13,16,17] The VZ has several critical functions, serving as
a barrier with polarized cells that regulate CSF composition,
mediating CSF flow via motile cilia, and secreting signals
involved in the development and physiology of the brain.[13]
Neuroepithelial cells are joined by tight junctions at their apical
surface, and while VZ ependyma loses tight junctions during
development, they continue to express adherens junctions on
their lateral surfaces.[14,15] Adherens meetings are primarily
composed of N‑cadherins, transmembrane proteins that
interact with catenin proteins and the actin cytoskeleton, as well
as other proteins and transcription factors.[18] N‑cadherins are
also involved in the regulation of catenin to modulate signal
transduction and developmental patterning.[18] Ependymal cells
elaborate cilia, organelles present on the surface of the cells that
beat in rhythmic waves. These cilia project into the ventricles,
contributing to the ependymal planar polarity. Ciliary beating
also contributes to CSF flow, especially in the narrowest parts
of the ventricular system, that is, the aqueduct,[13] although
myriad other mechanisms, such as pulsatility and pressure
gradients, influence CSF flow.[19]
Hydrocephalus
Hydrocephalus is a neurologic condition resulting from
an imbalance in CSF production and absorption, typically
producing ventricular enlargement and increased intracranial
pressure. [1,20,21] Traditionally, hydrocephalus has been
classified as communicating or noncommunicating,[22] with
communicating etiologies presumably resulting from the
reduction of the CSF transport or occult obstruction at the level of
the subarachnoid space.[23] Noncommunicating etiologies result
from an obstruction in the ventricular system, frequently at the
level of the aqueduct.[23] It is now recognized that hydrocephalus
is more complex and may have multiple points of potential
pathology or obstruction,[21] with impairment of CSF absorption
occurring anywhere in the cranial cavity. Hydrocephalus may
also be described broadly as congenital  (developmental)
or acquired. [1] Acquired hydrocephalus may result from
intracranial hemorrhage (e.g. subarachnoid or intraventricular
hemorrhage (IVH)) or other lesions developing after birth, while
developmental hydrocephalus may be genetic or syndromic in
origin or observed with anomalies, the pathogenesis of which
is not yet understood.[1] In North America, IVH is a common
cause of severe neurological injury in very preterm infants, and
resultant post‑hemorrhagic hydrocephalus (PHH) represents
the most common cause of pediatric hydrocephalus.[24,25]
Genetics of congenital/developmental hydrocephalus
Congenital hydrocephalus includes  (1) X‑linked
hydrocephalus with congenital aqueduct stenosis  (AS),  (2)
neural tube defects  (spina bifida),  (3) Dandy–Walker
syndrome,  (4) holoprosencephaly,  (5) primary ciliary
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S269
dyskinesia and other ciliopathies, and  (6) nonsyndromic
autosomal recessive hydrocephalus. Hydrocephalus has
been associated with other less common syndromes such
as Fried‑type syndrome; RAS‑opathies; and vertebral, anal,
cardiac, tracheoesophageal, renal, and limb anomalies plus
hydrocephalus  (VACTERL‑H).[1,26] The most frequent gene
mutations involved in these syndromes/pathologies are shown
in Table 1.
X‑linked hydrocephalus with aqueduct stenosis (XLH)
XLH is associated with a gene mutation in the neural cell
adhesion molecule L1‑CAM located on chromosome X.[1,26] It
is the most common genetic form of hydrocephalus (1/30,000
births).[20,27] L1‑CAM is a member of the immunoglobulin‑like
CAM family located on chromosome Xq28.[27,42] L1‑CAM is
a glycoprotein that mediates cell‑cell adhesion, playing an
important role in neural adhesion, migration, growth, and
morphology.[26,27] In 254 unrelated families, 211 mutations
in the L1‑CAM have been found, affecting different sites,[26]
with correlations between the mutation class and the severity
of the ventricular dilation:  (1) Class  I mutations are present
in the cytoplasmic domain of the protein,  (2) Class  II are in
the extracellular domain,  (3) Class  III provoke a premature
stop codon in the extracellular domain and loss of the protein
function, and (4) mutations in the noncoding regions.[26]
L1‑CAM mutations have long been linked to Corpus callosum
hypoplasia, retardation, adducted thumbs, spastic paraplegia,
and hydrocephalus (CRASH) syndrome.[43] Ventriculomegaly is
present in 100% of the cases, although its severity can vary.[26,27]
XLH is also commonly associated with AS, fused thalami, and
cerebellar lesions.[26,27] Adle‑Biassette et al.[27] reported that
89% of patients with XLH exhibited AS, probably from severe
ventriculomegaly and high‑pressure causing deformation.
However, it has also been suggested that impairment of the
cell L1‑CAM junctions is related to maldevelopment of midline
structures[26] [Figure 1].
Fried‑type syndrome is an X‑linked disorder caused by
mutations in the AP1S2 gene.[38] The clinical symptoms include
intellectual disability, basal ganglia iron deposition, and
hydrocephalus. AS and/or retrocerebellar or fourth ventricular
cysts have been detected in some hydrocephalic cases.[20]
Neural tube defects
Neural tube defects  (NTDs) occur due to failure of closure
of the neural tube during embryological development.
Myelomeningocele (spina bifida aperta (SBA)), which results
from impaired closure of the caudal neuropore, is the most
frequent NTD and occurs in 1–2 cases per 2700 births.[26] In
SBA, the meninges, dorsal spinal arch, and skin do not develop
properly; thus, the neural placode is exposed.[46] Hydrocephalus
is present in almost 80% of these cases and may be related to
genetic variations that cause the loss of the ependymal cell
polarity and ciliary beating[26] or genes related to neural tube
development.[46] However, there is no single genetic locus
mutation; its origin is likely a combination of multiple genes and
environmental factors. What is well established is that intake of
folate during pregnancy decreases the incidence of the disease.
It has been shown that genetic variants of single genes encoding
folate‑homocysteine metabolism or gene‑related interactions
between different folate pathways are risk factors.[46‑49] Notably,
 Garcia‑Bonilla, et al.: Genetics and molecular pathogenesis of hydrocephalus

Table 1: Genetic trisomy, duplication, and mutations associated with hydrocephalus.

Syndrome or pathology associated with hydrocephalusGene References
X‑linked hydrocephalus with congenital aqueduct stenosisL1‑CAM [26,27]
Neural tube defects FUZ, VANGL1/2, CCL2, others (gene involved in planar‑cell polarity) [1,28,29]
MTR, MTRR, MTHFR, MTHFD (folate‑related genes)
Walker‑Warburg Syndrome including Dandy‑Walker Trisomy 9, Duplication on 17q, POMT1, POMT2, POMGNT1, FKTN, [1,20,26,30,31]
syndrome FKRP, LARGE, ISPD, others
Holoprosencephaly and Porencephaly Trisomy 13, trisomy 18, SHH, ZIC2, SIX3, TGIF [26,32‑34]
Primary ciliary dyskinesia and other ciliopathies NEK10, GAS2L2, MCIDAS, TMEMg7, others [35,36]
Nonsyndromic autosomal recessive hydrocephalus CCDC88C, MPDZ, others [1,20,37]
Complex cystic malformations Deletion 22q13.3, CC2D2A, OFD1, KIF7, GLI3, GPSM2 [20]
Fried‑type syndrome AP1S2 [1,20,38]
RAS‑opathies NF1, KRAS, BRAF, PTPN11, SOS1, MAP2K1, NRAS, others [1,39]
Megalencephaly syndromes PIK3CA, CCND3, PIK3R2, AKT3 [20,40]
Posterior fossa crowding FGFR [20,30]
VACTERL‑H PTEN, FANCB [1,41]

in utero closure of SB reduces both the post‑natal incidence
of hydrocephalus and the need for shunting while also
positively impacting Chiari II malformation and neurological
outcomes.[50,51] These improvements further underscore the
complexity and multifactorial nature of the disease.
body to anchor the axoneme to the cell membrane. Another
motile cilium is only present during fetal neurodevelopment,
presenting 9 + 0 microtubular structure, and functioning as
an activator of a signaling cascade that establishes left‑right
sidedness and body laterality.[35]

Dandy–Walker malformation Motility is dependent on dynein proteins.[35] Primary ciliary

Dandy–Walker malformation  (DWM) is a common cerebral
malformation  (1/35,000 births) characterized by hypoplasia
and rotation of the cerebellar vermis; enlargement of
the fourth ventricle and posterior fossa; and rostrally
shifted position of the lateral sinus, tentorium, and torcula
herophili.[26,52] Hydrocephalus is present in 80% of DWM cases,
along with corpus callosum dysgenesis, schizencephaly, and
glial heterotopia.[53] DWM is associated with at least 18 types of
chromosomal abnormalities such as trisomy 9, but it has also
been associated with exposure to different viruses, alcohol,
or diabetes during brain development.[26,53] Mutations in the
genes POMT1, POMT2, POMGNT1, FKTN, FKRP, LARGE,
ISPD have been associated with the disease.[20,30] Furthermore,
DWM may also be linked to other genetic syndromes such as,
ectopic brain, and NTD.[53]
Holoprosencephaly (HPE)
HPE is a brain malformation caused by neural differentiation
abnormalities that lead to failure of separation of the left
and right cerebral hemispheres before neural tube closure.[54]
HPE incidence is 1/10,000 births. It may be associated with
hydrocephalus, DWM, and craniofacial abnormalities,[54] with
three types based on the grade of separation: alobar, semi lobar,
and lobar HPE.[26] Like other neurodevelopmental anomalies,
the pathogenesis of HPE may have genetic and environmental
influences or chromosomal abnormalities, such as trisomy 13,
18, or triploidy (25%–50%). The other 50% of the cases may be
related to glucose levels in mothers with diabetes, mutation
in 7‑dehydrocholesterol reductase, and at least 16 other genes,
including SHH, ZIC2, SIX3, and TGIF.[26]
Primary ciliary dyskinesia and other ciliopathies
With a prevalence of 1/15–30,000 births,[35] primary ciliary
dyskinesia originates from a defect in ciliary and flagellar
motility or orientation that causes cilia dysfunction. Motor cilia
are composed of an axoneme with 9 + 2 microtubules and a basal
dyskinesia in motor cilia is caused primarily by mutations in
genes that create immotile monocilia, that is, NEK10 or GAS2L2
genes encoding Hydin or polycystin‑1 proteins,[55,56] although
more than 50 genes have been identified.[35] Hydin regulates
dynein arm activity in the central pair of microtubules of the
9 + 2 axoneme in motile cilia;[57] thus, the mutation in this gene
can impair cilia motility.[58] MCIDAS mutations have been
shown to strongly correlate with hydrocephalus.[36]
In primary ciliary dyskinesia, hydrocephalus is usually present
with other pathologies, such as situs inversus congenital
heart disease, asplenia, or polysplenia. [55] It is thought
that hydrocephalus appears as a consequence of impaired
ependyma cilia beating in narrow CSF passages, provoking
AS.[36] As ependyma and choroid plexus are involved in CSF
production, changes in the CSF microenvironment secondary
to beating loss may affect CSF production, also contributing
to hydrocephalus.[36]
Nonsyndromic autosomal recessive hydrocephalus: Beyond X‑linked
hydrocephalus
Nonsyndromic congenital hydrocephalus comprises 2%–11%
of congenital hydrocephalus cases.[37] Distinct from XLH,
nonsyndromic congenital hydrocephalus includes the autosomal
recessive variations of the CCDC88C or MPDZ genes. [1]
CCDC88C encodes the actin‑binding protein DAPLE involved
in cell migration. Three domains have been described in DAPLE
mutations, generating an absence of the entire protein (families
I and III) or an absence of the binding domain (family II).[37]
Autosomal recessive hydrocephalus typically is characterized
by ventricular dilatation with an interhemispheric cyst, small
vermis, and enlarged posterior fossa.[37]
Hydrocephalus associated with other less common syndromes
Hydrocephalus associated with intracranial arachnoid cysts,
indicative of impaired CSF absorption within the meninges,[59]

S270 Neurology India | Volume 69 | Supplement 2 | November-December 2021

 Garcia‑Bonilla, et al.: Genetics and molecular pathogenesis of hydrocephalus
a b
c Interestingly, the disruption does not seem to correlate with
d e
Figure 1: Ventricular zone disruption in a human fetus with aqueductal stenosis
that became noncommunicating hydrocephalus postnatally. (a) L1CAM and
AQP4 detection in CSF samples from the hydrocephalic case and control. The
180 kDa form of L1CAM (red arrow and star) and other compounds reacting with
antiL1CAM, and the 35 kDa form of AQP4 (red arrow and star) are detectable in
the hydrocephalic CSF but not in the control. (b) Quantification by immune blot for
L1CAM and AQP4 shows increases in both proteins in the hydrocephalus case.
(c) Proposed mechanisms underlying ependymal denudation in spina bifida aperta
(SBA) patients. In control fetuses, the ependyma display normal gap (GJ) and
adherens (AJ) junctions formed by Ncadherin and connexin 43, respectively. In
hydrocephalic patients, Ncadherin and connexin 43 are abnormally accumulated in
the cytoplasm, creating dysfunctional adherens and gap junctions. In the aqueduct,
ependymal disruption and impaired synchronized cilia beating may induce stenosis.
Abbreviations: ER, rough endoplasmic reticulum; Nu, cell nucleus; TGN, transGolgi
network. (d, e) The pallium of a human hydrocephalic fetus showing (d) normal
ependyma with Ncadherin localized at the plasma membrane (full arrow), and
(e) disrupted ependyma with abnormal expression of Ncadherin (broken arrows).
Illustrations modified from Ortega et al.[44] and Rodríguez et al.[45]
has been related with mutations in the CC2D2A gene in Joubert
and Meckel syndromes and with deletion 22q13.3 Phelan–
McDermid syndrome.[20] RAS‑opathies, which include Noonan,
cardio‑facio‑cutaneous, and Costello syndromes,[20] originate
from mutations in the RAS pathways (e.g., NF1, KRAS, BRAF,
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S271
and PTPN11).[1,39] Hydrocephalus is present in these pathologies
and may be caused directly by the genetic abnormality or by
downstream effects on the brain itself. Similar to RAS‑opathies,
hydrocephalus may be observed in megalencephaly syndromes
and may have multiple causes, often related to mutations in
genes of the PI3K–AKT pathway.[40] Hydrocephalus is also
present in craniosynostosis syndromes where mutations in
fibroblast growth factor receptor genes have been identified.
Alterations in the skull or skull base configuration may create
an obstruction of CSF flow or reduced absorption from venous
hypertension.[30] VACTERL‑H is a syndrome related to FANCB
gene mutations and Fanconi anemia or excess chromosome
breakage.[20]
Molecular biology of hydrocephalus: Cell junctions and
ventricular zone disruption
The neuroepithelium lines the ventricular walls during brain
development and generates ependyma, which covers the mature
periventricular areas.[13] As described above, neuroepithelial/
ependymal cells are joined by adherens junctions formed by
N‑cadherin.[13] It has been shown that abnormalities in the cell
junctions during ependymal development can trigger or affect
the evolution of hydrocephalus.[13,23,60‑63]
Disruption of the VZ/SVZ in hydrocephalus is a common event
that involves the disassembling, disorganization, or loss of the
VZ cells.[60] The VZ/SVZ disruption follows a temporal and
spatial program: progression proceeds from caudal to rostral
regions, and during neurodevelopment, impairment begins
in early fetal stages when the tight junctions disappear.[60]
In human fetuses with SB, VZ disruption has been observed
in the pallium at 21–22 GW, with the disruption extending
throughout the lateral ventricles in fetuses by 40 weeks.[64]
ventricular volume but with the stage of neurodevelopment.[65]
Additionally, VZ/SVZ disruption seems to follow a common
pattern in different hydrocephalic etiologies. Neuroepithelium/
ependymal loss has been detected in cases with hydrocephalus
associated with SB[61,62,64] and communicating hydrocephalus,[66]
as well as IVH,[65] demonstrating that disruption is not only
present in congenital hydrocephalus but also in acquired
hydrocephalus, such as PHH.[65]
The alterations in cell junctions appear to contribute to
the developmental and physiological abnormalities of VZ
associated with hydrocephalus,[13] such as the alterations in
L1CAM and Aquaporin‑4 levels seen in human fetal‑onset
hydrocephalus  [Figure  1]. [44,45] These patients exhibited
abnormal cellular location of N‑cadherin and connexin 43 as
both proteins were detected in the cytoplasm of the cells instead
of the cell membrane.[61,62] This hypothesis has been tested in
chick embryos where the immunologic blockage of N‑cadherin
resulted in the loss of ependyma and formation of rosettes,[67]
and it has been observed in several experimental in vivo and
in vitro models.[60,67‑73]
In humans, VZ disruption is associated with anomalous
ependymal rosettes or heterotopia, [74] abnormalities in
neurogenesis that cause SVZ stem cell loss and disruption[60]
and AS.[13] Large rosettes have been detected in the areas where
VZ disruption is present.[62] These rosettes are characterized by
 Garcia‑Bonilla, et al.: Genetics and molecular pathogenesis of hydrocephalus
a group of cells organized in a “wheel” shape that lose their
polarity and cell junctions.[62] Subependymal rosettes near the
VZ disruption site have been detected expressing GFAP and
without N‑cadherin.[64] Heterotopia have been observed with
large clusters of βIII tubulin‑positive cells near the SVZ.[64]
Abnormalities in neurogenesis can be due to an impairment
of migration of neuroblasts caused by N‑cadherin defects,
displacing neural stem cells (NSC) and neuroblasts.[66] Human
fetuses with communicating hydrocephalus exhibit SVZ
NSC abnormalities resulting from the loss of the germinal
ependyma layer, disorganization of the SVZ, and abnormal
migration of the neuroblasts.[66] In human fetuses with IVH,
SVZ alterations also occur, including areas with NSC and
ependyma loss and translocation of cells into the lateral
ventricles[65] [Figure 1]. Finally, AS can occur from the loss of
neuroepithelium/ependyma[60]; when complete obliteration
takes place, noncommunicating hydrocephalus develops. The
subcommissural organ‑Reissner’s fiber complex  (SCO‑RF)
may play a role in AS.[22,75] The SCO creates a large mass of
negatively charged, sialylated glycoproteins, the RF, which
remains CSF‑soluble in normal conditions. In hydrocephalus,
the SCO‑RF is absent, possibly contributing to AS.[75]
It is likely that the denuded ependyma is replaced by reactive
astrocytes.[23,61,62,65,66] While experimental models clearly support
this response, the role of astrocytes in the development
and severity of hydrocephalus in humans is still unclear. In
congenital and acquired animal models, it has been shown
that the astrocytes covering the denuded ventricular walls
formed a new and organized layer.[69] Thus, they create a new
layer that may mimic the lost ependyma, expressing vimentin,
which lacks tight junctions, gap junctions, microvilli in contact
with the ventricle, the water channel Aquaporin‑4, caveolae,
paracellular permeability, and endocytosis.[69] More analyses
are needed in human fetuses to elucidate any possible role of
astrocytes in replacing the ependyma.
Inflammation can play an important role in the pathogenesis
of hydrocephalus, especially in acquired hydrocephalus such
as PHH. The levels of pro‑inflammatory molecules, such as
interleukins IL‑6, tumor necrosis factor‑alpha (TNF‑alpha), or
transforming growth factor‑beta (TGF‑beta) in the CSF correlate
with the severity of hydrocephalus.[76] Limbrick et al.[77‑80] have
shown promising candidates of biomarkers: IL‑6, IL‑8, CCL‑3,
TNF‑alpha, interferon‑gamma, or TGF‑beta; growth factors,
such as nerve growth factor; and cell adhesion and cytoskeleton
makers NCAM, tau, or GFAP. In addition, the neuropathological
examination of human fetuses has identified signs of
inflammation such as microglial activation and
reactive gliosis.[61,65,76] Pro‑inflammatory cytokines, such as
the ones mentioned above, can modulate epithelial barriers,
regulating paracellular permeability.[81] In this regulation, the
pro‑inflammatory cytokines modulate the internalization of
cell junction proteins.[81] However, the relationship between
inflammation and VZ disruption still needs to be understood,
and further studies are needed to focus on this relationship.
Future work on investigating hydrocephalus
Recently, novel genetic variants related to hydrocephalus have
been discovered, at once elucidating important mechanisms in
its pathogenesis, but also underscoring the complexity of the
disease. Molecular biological studies are urgently needed to
S272 Neurology India | Volume 69 | Supplement 2 | November-December 2021
rigorously investigate these novel pathways, including those
involved in inflammation, VZ disruption, alterations in cell–cell
junctions, and aberrant precursor cell biology. The development
and analysis of experimental models of hydrocephalus are a
fundamental step in this process. Further research should be
performed to uncover the genetic and molecular mechanisms
behind the pathophysiology of hydrocephalus to develop new
diagnostic and treatment strategies.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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 Review Article
Access this article online
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Website:
www.neurologyindia.com
DOI:
10.4103/0028-3886.332259
Department
of Biomedical
Engineering, Faculty of
Fundamental Problems
of Technology,
Wroclaw University
of Science and
Technology, Wroclaw,
Poland, 1Division
of Neurosurgery,
Department of Clinical
Neurosciences,
University of
Cambridge, Cambridge,
United Kingdom,
2
Institute of
Electronic Systems,
Warsaw University of
Technology, Warsaw,
Poland
#
These authors
contributed equally to
this work and share
joint first authorship.
Address for
correspondence:
Dr. Magdalena
Kasprowicz,
Department of Biomedical
Engineering, Faculty of
Fundamental Problems
of Technology, Wroclaw
University of Science and
Technology, 27 Wybrzeze
Wyspianskiego Street,
50‑370 Wroclaw, Poland.
E‑mail: magdalena.
kasprowicz@pwr.edu.pl
© 2021 Neurology India, Neurological Society of India | Published by Wolters Kluwer - Medknow S275
Mathematical Modelling in
Hydrocephalus
Agnieszka Kazimierska#, Arkadiusz Ziółkowski#, Magdalena Kasprowicz,
Afroditi Lalou1, Zofia Czosnyka1, Marek Czosnyka1,2
Abstract:
Background: Various studies highlight the significance of alterations in cerebrospinal fluid (CSF) and cerebral
blood flow  (CBF) dynamics in the pathogenesis of hydrocephalus and suggest the role of mathematical
modeling in studying these complex interactions.
Objective: This narrative review discusses mathematical models of CSF and CBF dynamics, including
Marmarou’s compartmental model of CSF spaces and a model of cardiac changes in cerebral arterial blood
volume. The diagnostic utility of CSF compensatory parameters is described along with current information
on secondary model‑based indices of cerebral hemodynamics in hydrocephalus.
Conclusions: Compensatory parameters derived from the model of CSF circulation have long been used
in the diagnosis and management of hydrocephalus patients. However, recent studies using mathematical
models of cerebral circulation also show alterations in CBF dynamics, and model-based indices of cerebral
hemodynamics, which can be calculated non-invasively using transracranial Doppler ultrasonography, can
be used as a complementary source of information about the state of the cerebrospinal space.
Key Words:
Cerebral blood flow, CSF compensatory parameters, CSF circulation, hydrocephalus, infusion test,
mathematical modeling, model‑based parameters of cerebral hemodynamics
Key Message:
Mathematical modeling of cerebrospinal fluid and cerebral blood flow dynamics can improve our understanding
of the complex relationships between components of the craniospinal space in hydrocephalus.
M athematical modeling offers the possibility
of improving our understanding of the
interdependencies between cerebrospinal
of model parameters with the use of external
volumetric manipulation  (the constant rate
infusion test) and demonstrate the importance of
fluid  (CSF) circulation, intracranial pressure– CSF compensatory parameters in the diagnosis of
volume relationship, and cerebral hemodynamics hydrocephalus. Next, we will discuss the model
in hydrocephalus. Various modeling approaches and secondary model‑based indices describing
have been proposed for hydrocephalus, dating cerebral hemodynamics. Finally, selected models
back to the early 1970s (as summarized in[1,2]), including both CSF and CBF circulations will be
and have included both representation of the presented.
biomechanical properties of the brain[3,4] and
compartmental analysis of the CSF spaces.[5,6] Marmarou’s Model of CSF Dynamics
More recently, an in vitro model incorporating
the ventricular system and the cranial and spinal The compartmental model of CSF dynamics
subarachnoid spaces has also been introduced.[7] proposed by Marmarou et al.[5]  (later modified
This review focuses on computational models slightly in [8–10]) describes the relationship between
of CSF and cerebral blood flow (CBF) dynamics production, storage, and reabsorption of CSF. Its
based on physiological signals monitoring. We electrical equivalent [Figure 1] is presented as a
will discuss different model approaches, starting circuit composed of a current source (corresponding
with a simple but clinically accepted model to CSF formation in the choroid plexus), a resistor
of CSF circulation  (Marmarou’s model). We and a diode (corresponding to CSF absorption in
will also present the method for identification
How to cite this article: Kazimierska A, Ziółkowski A,
This is an open access journal, and articles are distributed under the terms Kasprowicz M, Lalou A, Czosnyka Z, Czosnyka M.
of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 Mathematical Modelling in Hydrocephalus. Neurol
License, which allows others to remix, tweak, and build upon the work India 2021;69:S275-82.
non‑commercially, as long as appropriate credit is given and the new
creations are licensed under the identical terms. Submitted: 21-Jun-2021   Accepted: 18-Sep-2021  
Published: 11-Dec-2021
For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com
 Kazimierska, et al.: Mathematical modelling in hydrocephalus
Figure 1: Electrical model of cerebrospinal fluid circulation (adapted from [11])
the sagittal sinuses), and a nonlinear capacitor (corresponding
to compliance of the CSF space).[11]
In Marmarou’s model, the balance between the components of
CSF circulation under normal conditions is described by the
following equation:
 (1)
meaning that in the absence of additional disturbances,
production of CSF is balanced by its storage and reabsorption.
The rate of CSF production (Ip) is assumed to be constant. The
rate of CSF reabsorption  (Ir) is proportional to the gradient
between CSF pressure  (P) and pressure in the sagittal
sinuses (Pss):
 (2)
where RCSF is a parameter called resistance to CSF outflow.
The rate of CSF storage  (Is) is, in turn, proportional to the
compliance of cerebrospinal space (C):
 (3)
which depends on the gradient between CSF pressure (P) and
reference pressure (P0):
 (4)
where E is a parameter called cerebral elasticity. This
relationship is considered valid above a certain “lower
breakpoint pressure” above which the pressure–volume
curve becomes exponential; below that point, the relationship
is linear.
The combination of Eqs.  (1)–(4) produces the following
differential equation describing overall CSF circulation:
 (5)
where I (t) is the rate of external volume addition. It has been
successfully used in the analysis of different scenarios of
volumetric manipulation, such as bolus injection or constant
rate infusion, the latter of which is commonly employed in the
management of hydrocephalus patients.
Constant Rate Infusion Test
The constant rate infusion test is a type of volume–pressure
test, first described by Katzmann and Hussey, [12] where
intracranial pressure  (ICP) is monitored during addition
S276 Neurology India | Volume 69 | Supplement 2 | November-December 2021
of fluid into the CSF compartment at a constant rate. Fluid
infusion can be performed through any accessible CSF
compartment. In practice, this means either the lumbar
compartment or a subcutaneously placed reservoir connected
to an intraventricular catheter or shunt antechamber.
Currently, the infusion test is usually performed in a modified,
computerized version. Pressure and volume are monitored
throughout the test, starting with baseline recording before
infusion begins and up to the point when ICP reaches plateau
phase or the upper safety limit (e.g., 40 mm Hg); optionally, the
return to resting level can also be registered. The recordings are
then used in the solution to Eq. (5) for two periods:
• Before and during infusion (I (t) =0 for t < 0 and I (t) = Iinf
for t > 0):
(6)
• After infusion (I (t) =0 for t > 0 and P (t) = Pb + Iinf ∙ RCSF for
t = 0):
(7)
where E1 and E2 denote the elasticity during and after infusion,
respectively. It has been shown that the pressure–volume curve
is shifted upwards during the return to baseline after infusion
compared to the rise during infusion,[13] thus implying the
difference between coefficients E1 and E2 (i.e., the hysteresis
of the pressure–volume curve).
Interpretation of constant rate infusion test results
Figure 2 presents an example of infusion test recording with
analysis of test results. In the clinical setting, the profiles obtained
from constant rate infusion allow for a differential diagnosis
between specific types of hydrocephalus as well as diseases with
similar clinical image (e.g., brain atrophy versus normal pressure
hydrocephalus  (NPH)).[14] However, no single parameter has
been conclusively proven to provide the most information on the
patient’s condition and best indicate the response to shunting,
particularly in patients suffering from NPH.[15]
Resistance to CSF outflow  (RCSF, units: mm Hg/(ml/min)
quantitatively describes CSF drainage and is ascribed the
most predictive power in the management of hydrocephalus.
Typically, taking into account the age‑dependent nature of
this parameter, increased RCSF over  13 mm Hg/(ml/min)
in younger patients[16] or over  18 mm Hg/(ml/min) in the
elderly[17] indicates disturbances in CSF outflow.
Elasticity (E, units: ml − 1) theoretically describes the stiffness
of the brain and elevated elasticity over 0.18 ml  −  1 indicates
impaired pressure-volume compensation.[18]
Increases in baseline pressure (Pb, units: mm Hg) may indicate
disturbed pressure–volume compensation or elevated sagittal
 Kazimierska, et al.: Mathematical modelling in hydrocephalus

a b

c d
Figure 2: Illustrative example of constant rate infusion test results. Left column: a) intracranial pressure (ICP) recording and model approximation based on Eq. (6); c) pulse
amplitude of intracranial pressure (Amp) recording. Grey background indicates the time from the start to the end of infusion. Right column: b) pressure-volume relationship
and d) amplitude–pressure curve derived from ICP recording

sinus pressure, but the parameter has been previously shown
to be highly inconsistent in repeated measurements.[19]
The pressure and volume recordings obtained during
constant rate infusion further allow for estimation of the
pressure–volume and amplitude–pressure characteristics of
the intracranial system. The pressure–volume (P–V) curve [see
Figure  2b] describes the nonlinear relationship between
changes in volume (ΔV) and CSF pressure (P):
 (8)
The amplitude–pressure (AMP–P) curve represents the
relationship between the pulse amplitude of the ICP
waveform (AMP) and CSF pressure (P) [see Figure 2d]. The
increase in cerebral blood volume associated with heart
contraction can be considered equivalent to rapid bolus
addition of CSF volume at baseline pressure Pb, and the
relationship between AMP and mean pressure can be described
by the following equation:
 (9)
where Pp is the pulse pressure. The rise in AMP with increases
in mean ICP [see Figure 2c] has been demonstrated in previous
studies,[20,21] and the slope of the AMP–P regression line is
proportional to cerebral elasticity.[22]
Mathematical Models of CBF and CSF Dynamics
Frequent coexistence of hydrocephalus with cerebrovascular
disease and diminished ability to regulate CBF[23–26] suggest
the need to assess the state of cerebral hemodynamics in this
group of patients. It has been shown that when the disturbance
of CBF regulation is more severe than the derangement of CSF
circulation, shunt placement may not satisfactorily improve
the patient’s condition.[27] Therefore, to identify underlying
cerebrovascular pathology, clinical monitoring in hydrocephalus
patients should be extended with supplementary signals such as
arterial blood pressure (ABP) and transcranial Doppler (TCD)
cerebral blood flow velocity (CaBFV). It is of no additional risk
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S277
for the patient as the measurement of ABP and CaBFV can be
done noninvasively with satisfactory accuracy. ABP can be
monitored continuously via a miniature plethysmographic
cuff placed around the middle finger of the left hand held at
heart level. TCD is a noninvasive ultrasonographic technique
that uniquely measures local blood flow velocity in large
intracranial arteries. Constant vessel diameter and unchanged
angle of insonation are the two main assumptions that govern
the use of TCD as an indirect measure of CBF. Additionally,
TCD allows for the evaluation of cerebral arterial blood volume
changes (DCaBV). A mathematical model has been proposed
to assess ΔCaBV with TCD during a single cardiac cycle. A
detailed description of this model is presented below and in[28].
Pulse waveforms of ICP, ABP, and CaBFV form the input data
to these models and allow for derivation of secondary indices
that may provide valuable information on the state of cerebral
hemodynamics in hydrocephalus patients.
Non‑pulsatile cerebral blood flow model
Blood flows through two vascular compartments of the brain:
the first one is the cerebral arterial bed and the second one
consists of further parts of the cerebrovascular system, such as
arterioles, capillaries, venules, and veins. For simplicity, blood
flow through the first region is called cerebral arterial blood
inflow  (CaBF) and through the second level, cerebral blood
outflow (CBFout). Both CaBF and CBFout have a pulsatile character
but their pulse waveform shapes are different, resulting in
changes in cerebral blood volume (CBV) during a cardiac cycle.
These changes in CBV were first estimated by Avezaat and
Eijndhoven.[10] They measured the blood flow in the exposed
common carotid artery in dogs invasively using electromagnetic
flowmetry and proposed a methodology in which the change
in CBV over a single cardiac cycle is defined as
 (10)
where ΔCBV (t) is the change in cerebral blood volume during
a single cardiac cycle, t0 and t are the beginning and end of a

Kazimierska, et al.: Mathematical modelling in hydrocephalus
single cardiac cycle, respectively, CaBF (x) is cerebral arterial
inflow, CBFout (x) is cerebral blood outflow, and x is the variable
of integration.
The change in cerebral arterial blood volume (DCaBV) can be
estimated noninvasively using TCD and the continuous flow
forward (CFF) model.[28] This model assumes that CBFout has
low pulsatility when compared to CaBF,[29] and CBFout‑CFF can
be approximated by a continuous flow equal to CaBF averaged
over several cardiac cycles (mCaBF):
 (11)
When using TDC, cerebral arterial blood flow velocity CaBFV
is measured instead of flow; therefore, the recorded signal
should be multiplied by the unknown cross‑sectional area of the
insonated artery (Sa), which is assumed to be constant during
measurement.[30,31] Taking these assumptions into account, we
can rewrite Eq. (10) as
 (12)
where ΔC aBV CFF is the change in cerebral arterial blood
volume during a single cardiac cycle calculated from the CFF
model, Sa represents the cross‑sectional area of the insonated
artery (units: cm2), and mCaBFV is the mean value of cerebral
blood flow velocity CaBFV (units: cm/s).
The DCaBV calculated based on the CFF model signal has a
clear pulsatile component [Figure 3].
The development of a method for continuous ΔCaBV estimation
enabled the calculation of a set of indices describing cerebral
hemodynamics. The CFF model was also used for a detailed
investigation of parameters influencing the shape of ICP pulse
waveforms.[32] Results of that work suggest that amplitude
of pulse ICP in hydrocephalus patients  (in whom ICP was
increased by constant rate infusion study) depends more on
mean ICP than on the pulse amplitude of ΔCaBVCFF.
Figure 3: Pulsatile changes in intracranial pressure (ICP), arterial blood pressure (ABP), cerebral arterial blood flow velocity (CaBFV), and changes in cerebral arterial blood
volume (CaBV) calculated using the continuous flow forward (CFF) model
S278 Neurology India | Volume 69 | Supplement 2 | November-December 2021
”
Model‑based hemodynamic indices
Brain compliance is defined as the ability of the intracranial
system to tolerate or compensate for changes in intracranial
volume. There are two main measures of compliance in the
intracranial space: one describing the cerebrovascular arterial
bed (high-pressure compartment) and the second describing
the cerebrospinal space and venous system (low-pressure
compartment).  Compliance of the cerebrospinal space  (Ci)
refers to changes in the volume of the intracranial space with
regard to changes in ICP (Eq. (13)), whereas cerebrovascular
arterial compliance (Ca) represents the changes in arterial blood
volume in response to changes in arterial pressure (Eq. (14))[33]:
 (13)
 (14)
where AMP can be calculated either as the amplitude of the
fundamental component of the signal’s Fourier spectrum[28,34,35]
or the peak‑to‑peak amplitude of the signal in each heart
cycle.[36] Both compliances Ci and Ca can be calculated using
the CFF model.
During the constant rate infusion test performed in patients
with NPH, Ci obtained with the CFF model was shown to
decrease.[34] An example of percentage changes in Ci and Ca
during a controlled increase in ICP is presented in Figure 4.
The magnitude of relative change in Ci (from baseline to the
plateau phase of the test) was found to be associated with
greater brain elasticity and reduced compensatory reserve
at the phase of infusion.[34] Additionally, Ci can be calculated
continuously from heartbeat to heartbeat, reflecting the
relative changes in cerebrospinal compensatory reserve[34,36]
with a good correlation with the direct method of volumetric
manipulation.[36]
Analysis of changes in Ca and Ci conceptually enables continuous
monitoring of the Monro–Kellie doctrine.[37] This concept relies
 Kazimierska, et al.: Mathematical modelling in hydrocephalus

Figure 4: Illustrative example of changes in intracranial pressure (ICP), cerebral arterial blood flow velocity (CaBFV), pulse amplitude of ICP (AmpICP), pulse amplitude of
cerebral arterial blood volume (CaBV), intracranial compliance (Ci), and cerebrovascular arterial compliance (Ca) estimated using the continuous flow forward model (CFF)
during infusion test performed in a patient suspected of normal pressure hydrocephalus. Grey areas represent the baseline and plateau phase of the infusion test

on the assumption that changes in Ca and Ci in the same direction
may indicate a disturbance of the Monro–Kellie doctrine.
However, this approach has never been fully studied in
hydrocephalus.
Cerebral arterial time constant (τ) is a parameter which in theory
describes the time required the fill the cerebral arterial bed with
blood in reaction to a rapid change in ABP during one cardiac
cycle. Its significant advantages are independence of the vessel
diameter and calibration in units of time. It can be estimated as
the product of Ca and cerebrovascular resistance (CVR)[38]:
 (15)
where Ca is calculated from Eq.  (14). CVR stands for the
resistance of small cerebral arteries and arterioles and is
calculated as follows:
 (16)
where CVR is calculated according to Eq. (16), Ca according to
Eq. (14), and HR is heart rate expressed in beats per second.
This multiparameter method  (Eq. 17) was compared to the
traditional calculations of CCP and was found to be strongly
correlated with the “gold standard” method.[42,43] Unlike the
other methods, the new CCP formula never produces negative,
nonphysiological values.
Wall tension (WT) is a descriptor of active vasomotor tone.
According to Burton’s model, it can be calculated as follows[40,44]:
 (18)
Expanding this formula using CCP (Eq. 17), WT can also be
expressed as a function of brain hemodynamic parameters:
 (19)

where CPP is cerebral perfusion pressure estimated as mean
ABP – mean ICP. A study performed with the use of the CFF
model has shown that during the infusion test in NPH patients
τ gets shorter.[39] An example of changes in Ca, CVR, and τ is
presented in Figure 5. This shortening is the result of a significant
decrease in CVR prevailing over the change in Ca. A decrease in
CVR indicates vasodilatation of distal vessels in response to CPP
decrease to maintain constant CBF. As shown by the previous
study,[39] τ is not correlated with CSF compensatory parameters
but may be helpful in assessing the state of cerebrovascular
reactivity in patients with hydrocephalus.
Critical closing pressure (CCP) is the critical value of ABP
below which cerebral vessels collapse completely and CBF
ceases.[40] Historically, there have been various methods for
CCP calculation based on TCD measurements.[41] However,
recent development of methods for ΔCaBV estimation enabled
the introduction of a multiparameter formula for CCP that
includes mean values of ABP and ICP, CPP, Ca and CVR as
well as heart rate (HR):
 (17)
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S279
WT results from contractile tangential forces of smooth
muscles of arterial walls, and in experimental animals in steady
condition, with no hemodynamic maneuvers being applied,
WT has been proven to be positively correlated with CVR.[42]
Closing margin (CM) is defined as the difference between
ABP and CCP[45]:
 (20)
It can be considered as a safety margin for the cerebral
vascular system. When its value becomes zero or negative,
the probability of cerebral vascular collapse and flow cessation
increases.
During infusion tests, rising ICP causes CCP and WT to change
in opposite directions (CCP increases and WT decreases) while
CM remains relatively stable.[43,46] An example of the behavior
of CCP, WT, and CM is presented in Figure 6.
Integrated Mathematical Models
In the late 1980s, Ursino[47] introduced a multicompartmental
model encompassing both CSF and CBF circulation systems:
 Kazimierska, et al.: Mathematical modelling in hydrocephalus

the arterial–arteriolar cerebrovascular bed, cerebral veins,
CSF production and reabsorption, and the craniospinal
pressure–volume relationship. Similarly to Marmarou’s earlier
model, Ursino’s model uses an electrical analog to represent
the pressures  (including ABP, ICP, and CPP), flow rates,
resistances  (both cerebrovascular and to CSF outflow), and
compliances of the craniospinal system, and it allows for the
investigation of the interaction between CSF flow, cerebral
autoregulation, blood volume, and ICP. In subsequent studies
the model was employed, for instance, to demonstrate the
difference in model parameters between autoregulating and
non‑autoregulating patients.[48] A comparable tool for the
assessment of cerebral autoregulation was also proposed a
few years later by Czosnyka et al.[49] in the form of a hydraulic
model of cerebral circulation.
Similarly, the model proposed by Piechnik et al.[50] placed CSF
circulation in the wider context of its relationship with CBF
with specific focus on the regulatory ability of the left and right
hemispheres. The vascular arm of the model represents CBF
circulation starting with internal carotid arteries feeding the
input ABP signal into the circle of Willis. It further encompasses
anterior communicating and middle cerebral arteries leading
to the regulating arterial and arteriolar network, and then to
the intracranial venous compartment ending in a single jugular
vein. CSF circulation is in turn represented by the CSF flow
pathways from the ventricles to the cisterns and toward the
site of reabsorption in the subarachnoid spaces.
The model was used to investigate pulsatile CSF flow through
the aqueduct cerebri,[51] which is believed to increase in
hydrocephalus patients. The modeling study suggested that
CSF pulsatile flow depends on both cerebral hemodynamics
and pressure–volume compensation. During increases in
mean ICP, pulse amplitudes of ICP and CSF were both shown
to increase. This relationship, however, was inverted during

Figure 5: Illustrative example of changes in intracranial pressure (ICP), arterial blood pressure (ABP), cerebral perfusion pressure (CPP), cerebrovascular resistance (CVR),
cerebral arterial compliance (Ca), and cerebrovascular time constant (tau) estimated using the continuous flow forward model (CFF) during infusion test performed in a
patient suspected of normal pressure hydrocephalus. Grey areas represent the baseline and plateau phase of the infusion test

Figure 6: Illustrative example of changes in intracranial pressure (ICP), arterial blood pressure (ABP), critical closing pressure (CCP), wall tension (WT), and closing
margin (CM) estimated using the continuous flow forward model (CFF) during the infusion test performed in a patient suspected of normal pressure hydrocephalus. Grey
areas represent the baseline and plateau phase of the infusion test

S280 Neurology India | Volume 69 | Supplement 2 | November-December 2021

 Kazimierska, et al.: Mathematical modelling in hydrocephalus
increases in the resistance of the aqueduct cerebri and decreases
in the elasticity of the CSF space.
Conclusions
Historically, the origin of hydrocephalus has been associated
with disturbances in CSF flow pathways or imbalance
between CSF production and reabsorption. Consequently,
early mathematical models focused on the relationships
between the components of CSF circulation in an attempt to
assess the state of the intracranial space and the prognostic
value of various model parameters, mainly in predicting the
response to shunting. However, studies also suggest the role of
cerebrovascular factors in the pathogenesis of hydrocephalus,
and mathematical models of cerebral hemodynamics show
that many model‑based indices describing cerebral blood flow
are altered in hydrocephalus. The use of integrated models of
CSF and CBF circulation may provide additional information
on coexisting cerebrovascular pathology required to better
characterize hydrocephalus patients.
Financial support and sponsorship
The authors AK, AZ, and MK received support from the
Polish National Agency for Academic Exchange as part of
the International Academic Partnerships program. MC was
supported by NIHR Cambridge Biomedical Research Centre.
MC and ZC were supported by Revert Project, Interreg
France (Channel Manche) England, funded by ERDF.
Conflicts of interest
MC has a financial interest in part of the licensing fee of
ICM + software (https://icmplus.neurosurg.cam.ac.uk) used
for infusion studies. Other authors declare that they have no
conflict of interest.
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 Review Article
Access this article online
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DOI:
10.4103/0028-3886.332282
Department of
Diagnostic Imaging,
Hospital for Sick
Children, University of
Toronto, Canada
Address for
correspondence:
Pradeep Krishnan,
Pediatric Neuroradiology,
Diagnostic Imaging,
The Hospital for Sick
Children, 555 University
Avenue, Toronto, Ontario,
Canada M5G 1X8
Email: pradeep.krishnan@
sickkids.ca
© 2021 Neurology India, Neurological Society of India | Published by Wolters Kluwer - Medknow S283
Hydrocephalus in Children:
A Neuroradiological Perspective
Charles Raybaud, Pradeep Krishnan
Abstract
Concepts about the production, absorption, dynamics, and physiological roles of cerebrospinal fluid (CSF) have
dramatically changed over the recent decades. This article will review these new concepts and detail how they
must be used for a better assessment and a better understanding of the various aspects of hydrocephalus
by using neuroradiological tools.
Key Words:
CSF, CSF pathways, development, hydrocephalus, imaging, physiology
Key message:
Hydrocephalus is not only a disease by itself but also a mechanical complication of many different conditions,
which all result in the fact that the cerebrospinal fluid (CSF) compartment becomes actively enlarged at the
expense of the brain tissue. The essential nature of hydrocephalus is an accumulation of fluid with progressive
compression of the brain, and CSF must be diverted to preserve it. The primary diagnosis is simple and consists
of identifying an increased ventricular size and effacement of the subarachnoid spaces, macrocephaly often
in children, and an obstruction somewhere along the CSF pathway. However, because hydrocephalus can
be caused by many diseases, the evaluation is more complex in individual patients.
F or decades, it was understood based on
the concepts formulated by Dandy and
Blackfan[1] early in the last century: There is a
the mechanism of the ventricular enlargement
could be the “pumping” force of the pulsating
choroid plexuses.[3] Di Rocco and Pettorossi[4,5]
bulk flow of CSF from the secreting ventricular confirmed that the force generated by the
choroid plexuses toward peripheral absorption vascular pulsatility could play a significant part
sites, along the ventricular and subarachnoid in hydrocephalus. This was further supported
pathways; obstruction anywhere along this in the 1990s when MR imaging demonstrated
path would cause CSF accumulation upstream, noninvasively in human subjects that the
that is obstructive hydrocephalus; communicating pulsatile, arterial stroke-related force is much
hydrocephalus was the term used when no stronger and displaces much larger CSF volumes
ventricular obstruction is found. than the secretion–absorption flow.[6,7]
Pathogenesis of Hydrocephalus: The discovery of the water channels Aquaporins
Evolving Concepts (AQP) provided the cytologic support to the
concept that water can be actively transported
New facts have emerged after Dandy and across the interfaces between CSF spaces,
Blackfan proposed the initial concepts. In the parenchyma, and vessels.[8] The distribution of
1950s, Bering demonstrated that heavy water AQP4 along the CSF/brain/vascular interfaces
D2O could exchange freely between the CSF is consistent with a significant role in the CSF and
spaces, the parenchyma, and the blood, [2] interstitial fluid (ISF) physiology.
showing that water can easily be transferred
in and out of the parenchyma, which could Secretion and Absorption of the CSF
therefore participate in both the production
and the absorption of CSF. Later, in other Classical estimation of the total CSF volume of
experiments on obstructive hydrocephalus CSF was estimated to be 50 ml in newborns,
without or with plexectomy, he suggested that 60–100 ml in children, and approximately
This is an open access journal, and articles are distributed under the terms How to cite this article: Raybaud C, Krishnan P.
of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 Hydrocephalus in Children: A Neuroradiological
License, which allows others to remix, tweak, and build upon the work Perspective. Neurol India 2021;69:S283-91.
non‑commercially, as long as appropriate credit is given and the new
creations are licensed under the identical terms. Submitted: 06‑Aug‑2021   Revised: 10-Sep-21
Accepted: 13-Sep-2021   Published: 11-Dec-2021
For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com
 Raybaud and Krishnan: Hydrocephalus in children
150 ml in adults, including a ventricular volume of 25 ml
(smaller in infants at 10–15 ml). New measurements using
volumetric MR imaging in adults provide much higher values:
approximately 150 ml, or even 230–270 ml,[9] for the intracranial,
extraventricular spaces, and 100–120 ml for the spinal spaces.
This means that intracranially, just by pushing the brain to fill
the pericerebral spaces, the ventricular volume may increase
considerably, the cerebral volume remaining unchanged.[10] The
daily production of CSF is estimated at 500–600 ml in adults
with a production (and absorption) rate of approximately
0.35 ml/min; with the revision of the volume estimations, it
may be even less. Relatively constant between individuals
and between normal and hydrocephalic subjects, this average
rate may vary between 0.05 and 0.78 ml/min in adults with
“communicating hydrocephalus” (higher in the second part of
the night) and between 0.25 and 0.40 ml/min in hydrocephalic
5–13-year-old children, lowest at 0.25 ml/min in 1-month to
8-year-old patients;[11] the production increases in proportion
to the size of the brain as development proceeds [Table 1].
The CSF and the substances it contains are secreted by the choroid
plexuses, but fluid produced by the rest of the brain parenchyma
makes a significant contribution. CSF includes 99% water and
ions (Na+, K+, Ca++, Mg++, Cl−, and HCO3−), proteins, amino acids,
creatinine, urea, lactate, phosphate, and glucose.[12,13] Protein
concentration is higher in newborns, especially preterm, and
glucose concentration is slightly lower. In addition to acting
as a protective cushion for the brain, CSF serves as a transport
vehicle for neurotrophic substances, signaling molecules,
neurotransmitters, and other metabolites, to and from the brain.
CSF is “analyzed” by the circumventricular organs, devoid of
CSF–brain and blood–brain barriers, the hypothalamus reacting
in response to the changes[14]
Choroid plexuses are the primary source of CSF, producing
60%–90%; the remaining 10%–40% is produced by the brain
and cord parenchyma. Choroid plexuses secrete the CSF in two
steps: first, a passive exudation from the fenestrated vascular
endothelium into the plexular interstitium; then, a regulated
transport of water, ions, and larger molecules across the
epithelial layer into the ventricle.[12,15] The passive exudation
in the plexular stroma decreases when ICP increases but
never stops completely (the arterial pressure is superior to
the ICP as long as a blood flow is maintained). It is regulated
by vasoactive substances (norepinephrine, angiotensin II,
and serotonin). The active secretion uses ATP-hydrolysis
to generate a unidirectional flux of ions across the plexus
epithelium,[16] regulated by neuropeptides such as choroidal
arginine vasopressin (AVP) and atrial natriuretic peptide
(ANP).[17] The secretion rate is relatively insensitive to osmotic
pressure changes.[18] Water is conveyed by the cellular water
transporter AQP1 found in high concentration at the apical
side of the choroid epithelial cells.[18–20]
Nutrients, proteins, metabolic precursors, and neurotrophic
factors are also secreted by the epithelium; this secretome is
both regionalized (different in the forebrain and the hindbrain)
and evolutive according to the stage of brain development.[12]
The contribution of the brain parenchyma
Choroid plexectomy does not result in the absence of CSF.[21]
In obstructive ventricular hydrocephalus, the extracerebral
S284 Neurology India | Volume 69 | Supplement 2 | November-December 2021
CSF has to be produced by the surface of the brain and cord
(mostly the VRS) as water molecules exchange diffusely across
the brain surface. In the case of an osmolar shift, this exchange
may represent a significant contribution to the total volume
of CSF.[22] ISF and CSF share a similar composition and form
a single brain extracellular fluid compartment.[13] The water
channel AQP4 is densely expressed in the ependyma, in the
subependymal astrocytic end-feet, around the parenchymal
capillaries, and the subpial glia limitans of the brain surface
and VRS, and regulates the transport of water.
The VRS form blind channels that originate in the depth of the
parenchyma and open at its surface. This pattern, reminiscent
of the lymphatic channels, suggests that they may drain
the parenchymal ISF into the arachnoid spaces. The term
“glymphatic” (for glial lymphatic) has been proposed to
designate this function.[23] Within the VRS, the pia-arachnoid
sleeve is fenestrated for the fluid to circulate from the subpial
space to the PVS.[24] Whether arterial and venous VRS together
form “loops,” the pulsating wave in the arterial VRS driving
water toward the parenchyma and the venous VRS draining it
toward the arachnoid space[25] is controversial. In the absence
of a valve at the opening of the arterial VRS, the pulsation may
facilitate diffusion but not convey water inward. The current
evidence suggests that the AQP4 channels transport water from
the ISF to the VRS and from the VRS to the arachnoid space.
The absorption rate of CSF in a normal situation equals its
production rate. An intrathecal infusion study in adults
found that absorption does not occur at or below 68 mm
H2O and increases linearly with an increasing ICP, to reach
approximately 1.5 ml/min at a pressure of 250 mm H2O (the
pressure was not measured above that level).[26] Thus, the range
of absorption capacity is sufficient as long as the absorption
sites are efficient. The arachnoid villi are considered the main
CSF absorption site, depending on the CSF-venous sinus
hydrostatic pressure gradient. Histology suggests one-way
valves that open at a pressure difference of 20–50 mm H2O[27]
(pinocytosis has also been proposed).[28] In addition to the villi,
which carry fluid into the veins, other transdural sites seem to
move fluid toward dural and peridural lymphatics: dural clefts
along the parasagittal dura (different from the classic villi),[29]
venous plexuses of the cavernous sinuses or around the internal
carotid artery and pituitary gland,[30] cribriform plate along
the olfactory nerve toward the nasal mucosa,[31] optic nerves
sheaths,[32-35] and other cranial and spinal nerve outlets with
their arachnoid villi and lymphatics.[27] It is unclear whether
these different pathways are hierarchic, depend on age and
maturation, or are simply synergetic, but all may contribute
to the CSF absorption. Importantly, all are “passive” routes
dependent on a CSF-peridural pressure gradient only.
Hydrodynamics of the CSF and Hydrocephalus
The translation of fluid from one point to another is referred
to as a bulk flow; a to-and-fro motion of fluid without net
translation is called an oscillating (or pulsatile) flow. The
Brownian displacement of molecules within a fluid is called
diffusion; convection describes thermal energy-driven currents
within a fluid. In the case of the cerebral ventricles, a cilia-
directed near-wall flow is also observed. Bulk flows, pulsatile
flows (driven by vascular pulsatility), and cilia-directed
 Raybaud and Krishnan: Hydrocephalus in children

near-wall flows have been associated with hydrocephalus. Table 2 Classification of obstructive hydrocephalus with
For the latter, this was in rodents, and it is likely not to apply imaging findings.
to humans, as will be described below. Instead of one single
global bulk flow, it is logical to assume that several segmental bulk Magnetic resonance imaging
flows coexist in a sequential manner within the lateral, third, Magnetic resonance (MR) imaging is the best tool to investigate
and fourth ventricles around the convexity and in the spinal hydrocephalus, its causes, and its consequences. It investigates
canal [Figure 1 a,b]. the specific morphologic features of hydrocephalus, the
site(s) of obstruction (if any), the parenchymal effects of
Table 1 (approximate evaluations from literature data). hydrocephalus and/or the causal disease, and appreciates
the CSF dynamics. The imaging protocol, which would also
These pathogenetic events explain the two main types of show a mass or infection, is relatively simple. (1) Tridimensional
hydrocephalus: “chronic” (ICP close to normal) and “acute” millimetric T1 with reformatting in any plane provides the
(ICP elevated). Chronic hydrocephalus develops primarily general brain morphology. (2) Coronal T2-Fast Spin Echo (FSE)
due to a decreased compliance (obstructive) or a decreased demonstrates the ventricular changes: temporal horns, septum
absorption (nonobstructive or absorptive), the participation pellucidum, hippocampal commissure, pericerebral spaces,
of an absorption defect or restricted compliance, respectively, the normally slit-like third ventricle. We find that measuring
being only marginal. Acute hydrocephalus develops when the longest transverse atrial diameter of the most prominent
both compliance and absorption processes are severely lateral ventricle provides the most reliable quantification of the
compromised together [Table 2]. ventriculomegaly as the dilatation is usually more prominent
posteriorly in pediatric hydrocephalus. (3) Sagittal thin T2-
Neuroimaging of Hydrocephalus: The Tools FSE provides the gross morphology of the midline structures:
third ventricle with the lamina terminalis, the supra-optic,
In infants and young children, macrocrania is the main presenting infundibular, and (variable) suprapineal recesses, and tuber
symptom of chronic hydrocephalus (low ICP) with diverse cinereum normally convex upward; aqueduct and its CSF
possible neurological manifestations. Even though cases flow-void; fourth ventricle, cistern magna with the often
of arrested hydrocephalus have been documented, slow “hanging” choroid plexus, and prepontine cistern with the
deterioration and acute decompensation are more common prominent, basilar artery-related flow-voids. (4) Submillimetric
in the long term. Factors related to potential cerebral damage sagittal steady-state T2 imaging (FIESTA/CISS sequence) is
are the patient’s age at the onset of the hydrocephalus, its vital for obtaining clear images of thin membranes in the
duration, and its etiology. An acute presentation typically ventricles, aqueduct, or cisterns [Figure 2]. It is crucial to
includes increased ICP, with signs and symptoms related to evaluate the patency of the interpeduncular cistern before
the etiologic disease. Macrocephaly is not expected, but the
separation of the suture is often seen in children. Hyperacute
hydrocephalus describes a situation in which a steep increase of Table 1: Physiology of CSF circulation (1)
the ICP results in the ventricular entrapment of CSF: a rapidly Level Volumes Ratio
developing brain swelling (usually trauma or acute infection) (approximative)
compresses the midbrain, preventing the CSF to escape into Cerebral Blood Flow 650 ml/min 100%
the arachnoid spaces while blocking absorption. Because of the (50 ml/100 g/min,
brain 1300 g)
brain swelling and the rapidity of the process, the ventricles
CSF displaced C2‑C3 (= whole brain) 39 ml/min 6%
cannot enlarge but become rounded. An important point in this
Tentorial Incisura (= 14.3 ml/min 2.23%
short clinical introduction is that clinical evidence of an increased
forebrain)
ICP is an absolute neuroradiological emergency. Ideally, MRI, or
Aqueduct (= lateral + 1.7 ml/min 0.26%
CT if MRI is not immediately available, must be performed to
third ventricles)
identify the cause of intracranial hypertension and appreciate
CSF absorbed 0.35 ml/min 0.05%
the presence of drainable hydrocephalus. (evaluated)
Blood displaced 611 ml/min 94%

a b
a b
Figure 1: Bulk flow patterns. a) Classic model: single bulk flow from the choroid
plexuses to the convexity and dural sinuses; b) Multiple segmental bulk flows Figure 2: FIESTA, sagittal midline. a) Normal brain; b) Choroid plexus cyst of the
reflecting the multiple sites now recognized of CSF production and absorption. third ventricle.

Neurology India | Volume 69 | Supplement 2 | November-December 2021 S285

 Raybaud and Krishnan: Hydrocephalus in children
Table  2: Morphologic/pathogenetic classification of obstructive hydrocephalus with imaging findings(1)
Timing Vasc bed Ventricular size
Hyper‑acute Sudden ↓↓↓
Progressive Weeks months ↓↓
Chronic Months years ↓ ↑
Arrested Years = ↑
a ventriculostomy, and the patency of the stoma after it. (5)
Axial FLAIR shows the axial ventricular morphology and the
parenchyma. (6) If a mass or infection is seen, diffusion-weighted
imaging (DWI) and post-contrast T1 imaging must be done to
characterize the mass. Blood and blood products (hemosiderin)
are best shown on T2* gradient echo (GE) or susceptibility-
weighted imaging (SWI) (better).
For a long time, follow-up studies have used low-radiation
quick CT acquisition because it is fast and alleviates the need
for sedation/anesthesia. However, because of mounting
concerns regarding the use of ionizing radiations in children],
fast MR-scanning imaging has been developed using single-
shot, ultrafast imaging sequences. These heavily weighted T2
images are adequate for assessing the ventricular/cisternal
size and morphology and identifying a shunt’s position. They
have poor sensitivity and specificity for parenchymal changes.
It is generally considered that T2-FSE in the clinical setting
is quite good for assessing the aqueductal flow-voids, which
become prominent whenever the CSF velocity or amplitude
is increased. Many dedicated sequences have been developed
to evaluate and even attempt quantification of these CSF
movements. Yet the CSF oscillations depend on a combination
of different factors such as the strength and volume of the
arterial stroke, the degree of wakefulness, the distal vascular
and thecal compliance, and the CSF pressure; thus, the
reliability of the measurements in individual patients is low.
¹H MR spectroscopy is used to identify changes in energy
metabolism. Arterial spin labeling (ASL) perfusion can be used
to investigate the blood flow noninvasively.[36,37] Positive
contrast cisternography or ventriculography have been suggested
and are considered safe[38]; however, they have failed to gain
acceptance as the trend in brain imaging is toward minimal
invasiveness. MR venography (MRV) may demonstrate an
acquired or developmental venous compromise, primary or
secondary to the hydrocephalus. SWI is used to demonstrate
blood and blood residues. Diffuse tensor imaging may show
better the condition of the parenchyma.[39] MR elastography
is a new technique that may provide information about the
condition of the parenchyma.[40] Finally, as hydrocephalus may
occasionally be caused by or associated with a spine lesion
(tumor or malformation or syringomyelia), dedicated spinal
imaging may be necessary to complete the evaluation.
In neonates and young infants, the imaging strategy is
essentially the same as in more mature children; however,
some technical points should not be overlooked. The
sequences must be adapted to the lack of myelin; FLAIR
sequences in this indication are essentially noncontributory.
In normal conditions, the total volume of CSF displaced by
the arterial systolic stroke is directed peripherally (pulsations
of the fontanelle) rather than caudally. Hence, the lack of
S286 Neurology India | Volume 69 | Supplement 2 | November-December 2021
Perivent edema Skull Outcome
= no = arrest
↑ yes =/↑ decompensates
no ↑ slow ↑
no ↑/= stable?
flow void within the aqueduct is a normal finding. In the
background of incomplete subcortical connectivity, the deep
medullary tributaries of the subependymal veins appear more
extensive across the thickness of the cerebral mantle relative
to the territory of the subcortical veins. As a consequence,
periventricular interstitial edema also seems more extensive
than in a mature brain. In addition, diffusion of the interstitial
water may be easier in the “soft” immature tissue. Hence,
periventricular edema is more challenging to recognize against
the infantile white matter’s background of normal high-water
content. On the contrary, fibrotic changes of the ventricular
walls may appear better as a periventricular rim of low T2
signal contrasting with the bright signal of both the CSF and
the white matter.
CT scanning is still a commonly used modality to evaluate
hydrocephalus; it is fast and straightforward, and acquisition
data are easily reformatted in multiple planes on modern
scanners. Periventricular interstitial edema is readily apparent,
and calcification may appear better on CT than on MR. Mass
effects responsible for hydrocephalus are easily recognized,
and contrast enhancement helps characterize the pathology.
Still, the diagnostic yield and versatility of CT are much less
than those of MR, and CT can expose children to significant
doses of ionizing radiation. An initial evaluation of the brain
should always be based on MR. If CT is to be used for follow-
up, implementing a low-dose technique limits the assessment
to ventricular and pericerebral spaces and position of the
shunt only.
Head ultrasonography (US) is the primary modality of choice
for screening infants suspected of having hydrocephalus. It
is noninvasive, can be performed at the bedside, and gives a
good evaluation of the ventricular size and morphology. It is
sensitive (although less specific) to parenchymal abnormalities
and, along with Doppler, can provide an efficient functional
assessment of the vasculature. However, US is limited to
when the fontanelles are open, and it does not provide nearly
as comprehensive a presurgical assessment of hydrocephalus
as MRI. However, monitoring of intracranial pressure by US
is possible[41]
Neuroimaging Features of Hydrocephalus
The characteristic triad of hydrocephalus comprises ventricular
rounding and dilatation, effacement of the pericerebral spaces, and
macrocephaly. Changes in the temporal horns are more specific
than a diffuse enlargement of the lateral ventricles: the horn
is rounded, the choroid fissure is distended, the hippocampus
is displaced and compressed infero-medially, the Sylvian
fissure is effaced (in atrophy, the roof and the floor would be
roughly parallel, the hippocampus would not be displaced,
and the Sylvian fissure would be prominent). In hyperacute
hydrocephalus, a ventricular dilatation is typically absent
 Raybaud and Krishnan: Hydrocephalus in children
because of brain swelling, but ventricular rounding is present,
especially of the temporal horn [Figure 3]. In all, the tension of
the lateral ventricles modifies the appearance of the midline:
the lateral ventricles are more dilated than the third ventricle,
and the third ventricle roof is pushed downward. The corpus
callosum is stretched, thinned, arched upward, but not the
columns of the fornix; thus, the septum pellucidum is stretched
and maybe torn. The hippocampal commissure (psalterium),
normally transverse, becomes verticalized on each side of
the midline; thus, the posterior part of the fornix seems to be
detached from the undersurface of the splenium. In rare cases of
chronic severe obstructive hydrocephalus (usually aqueductal
stenosis), the ventricular anatomy may be compounded by a
ventricular diverticulum: the thin infero-medial portion of one
atrial wall may extend through the choroid fissure, behind
the thalamus, into the quadrigeminal and supra-cerebellar
cisterns. The midbrain may become compressed with the risk of
significant neurological complications; such diverticula should
not be mistaken for quadrigeminal cistern cysts: coronal images
demonstrate that they are continuous with the lateral ventricle.
Similarly, the weaker lamina terminalis, tuber cinereum, pre-
and retro-chiasmatic recesses of the anterior, and hypothalamic
half of the third ventricle bulge into the adjacent cisterns. The
adjacent dorsum sellae may be eroded, and the tuber may wrap
the head of the basilar artery. Moreover, the proximal aqueduct
is also dilated when the obstruction is in its distal portion. On
axial images, the dilatation of the anterior third ventricle in
hydrocephalus should be differentiated from the huge and
more global rounding of the whole third ventricle produced
by a suprasellar leptomeningeal cyst. When hydrocephalus
is chronic and severe, the tuber cinereum may rarely rupture
spontaneously, allowing CSF to escape to the subarachnoid
space.[42]
The cerebral aqueduct of Sylvius is usually a narrow craniocaudal
curved channel that connects the third and fourth ventricles
below the quadrigeminal plate. Occlusion may be intrinsic
(ependymal, usually post-inflammatory) or extrinsic
(tegmental or tectal mass lesion, extra-axial mass). In some
instances, aqueduct stenosis may result from compression by
expanded temporal lobes. The flow-void usually observed on
Figure 3: CT scan of a 13-year-old, acute meningitis. Mild ventricular dilatation but
clear ventricular rounding with effacement of the peri-cerebral spaces.
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S287
the sagittal midline T2 FSE image disappears if the aqueduct
is occluded but may increase if it is narrowed. The aqueduct
may be dilated when the obstruction is in the fourth ventricle
or more caudal. The amplitude of the aqueduct CSF pulsations
may then be increased, like in nonobstructive hydrocephalus,
because the arterial pulsatility is redirected medially or because
of a decreased meningeal compliance (“rebound effect”).
The size of the fourth ventricle depends on the site of the
obstruction: normal when the block is located above it,
dilated if it is below. It may be normal in nonobstructive
hydrocephalus: a periventricular dilation does not necessarily
suggest aqueductal stenosis. However, in most cases, the fourth
ventricle (and typically also the basal cisterns) is mildly dilated.
The normal size of the cisterna magna is variable, but its upper
limit should not extend beyond the torcular; even if it does, a
large cisterna magna should not be mistaken for a cyst if no
mass effect is observed on the vermis, fourth ventricle, brain
stem, and anterior cisterns. In nonobstructive hydrocephalus,
a posterior rotation of the vermis may occur, which is not
a malformation but just hydrocephalus. Finally, the fourth
ventricle may become hugely dilated when both in-flow and
out-flow are obstructed (isolated fourth ventricle).
The cisternal spaces are always effaced over the convexity when
a hydrocephalic process actively distends the ventricles:
their appreciation is an essential part of the diagnosis. This
effacement is the reciprocal of the ventricular dilatation and
depends on the site of the obstruction. In nonobstructive
hydrocephalus in a mature child, the basal and posterior fossa
cisterns may be prominent. However, in an infant, the vault
adapts to the hydrodynamic force and the enlargement is
located over the frontotemporal convexity. When the cisterns
are obstructed by diffuse arachnoid fibrosis, they become
multiloculated, a common finding in young children because
of the high incidence of hemorrhages, infections, and tumor
dissemination. In such cases, high definition CISS/FIESTA
imaging is mandatory for a proper assessment of these patients.
It may be challenging to identify on imaging; however, brain
parenchyma is affected by hydrocephalus,[43–48] with a high
prevalence of epilepsy. The changes in low-ICP hydrocephalus
are minor and can be repaired more easily as compared to
those of high-ICP hydrocephalus. Loss of the ependymal cilia
and progressive flattening of the ependymal cells are followed
by the disruption of the ependymal lining, notably over the
septum pellucidum.[49] Whether the ependyma may reconstitute
itself is not clear.[44,50] Subependymal proliferative gliosis may
develop, and the regenerative power of the subventricular zone
may be compromised. Circumventricular organs are damaged,
along with the rest of the ependyma. Choroid plexuses
degenerate and become sclerotic, possibly with decreased
secretory activity.[49] Within the parenchyma, the microvascular
density and the cerebral blood flow are decreased, with a
global increase of the extracellular spaces.[44,46,49,51,52] Increased
water content may relate to poor ISF absorption and, later, to
a developing process of atrophy; it affects neurotransmitters
and metabolites’ transport and prevents an appropriate
removal of waste products. Inflammation with macrophages,
astrogliosis, and loss of oligodendrocytes with decreased
myelin density is noted. Axons become stretched, especially
in the periventricular regions (e.g., fornical system), and may
 Raybaud and Krishnan: Hydrocephalus in children
later be lost. In children, the posterior part of the hemispheres
is the most severely affected, white matter and cortex.[45] In
very early-onset hydrocephalus, this may be associated with
an abnormal gyration (stenogyria) and gray-matter heterotopia.
Although many of the acute changes noted in progressive
hydrocephalus (interstitial edema, demyelination, vascular
compromise, and axonal loss) are reversible if shunting is
performed in a timely fashion, some (ependymal damage,
gliosis, and abnormal myelination, including aberrant
myelination of glial cells) may persist.[49] Demyelination and
axonal degeneration have a similar MR appearance: a ribbon
of bright T2/FLAIR signal in the paraventricular white
matter. Axonal degeneration does not necessarily imply
neuronal loss,[44,49] and damaged axons may regrow, with a
return to a normal appearance. This may be spectacular in
infants whose posterior cerebral mantle was compressed to
a few millimeters before shunting. A rare effect of chronic
long-lasting hydrocephalus is “ventricular disruption,” which
occurs when a local rupture of the ventricular wall allows the
progressive development of a CSF-filled cleft that dissects the
white matter open.
Acutely, high-ICP hydrocephalus is characterized by
periventricular interstitial edema, an accumulation of interstitial
water in the periventricular white matter [Figure 4]. Rather
than an increased outflow of fluid from the ventricle to the
parenchyma (which would relieve the ventricular pressure), it
results from the effacement of the lumen of the subependymal
veins preventing the normal parenchymal drainage.[49] It
is a complication of hydrocephalus, not a compensatory
process; it increases the intracerebral volume and therefore
the mass effect, and causes local damage to the cerebral
parenchyma.[44,49] This is best shown on axial FLAIR images:
enlarged ventricles with stretched subependymal veins
and bright-appearing ribbon of periventricular interstitial
edema. Diffusion-weighted images would reveal increased
water motion. It is not seen in hyperacute hydrocephalus
(water cannot accumulate in a short period) nor in chronic
hydrocephalus with normal ICP. On CT, it appears as a
periventricular hypodensity; the ventricular margins may
appear indistinct.
Figure 4: MR, axial FLAIR. Dilated ventricles with periventricular interstitial edema
(posterior fossa tumor)
S288 Neurology India | Volume 69 | Supplement 2 | November-December 2021
Hydrocephalus may lead to downward herniation of the mesial
temporal structures along the free edge of the tentorium
toward the posterior fossa, compressing the midbrain and
the aqueduct and the vessels in the process, with resulting
ischemia/infarction. In case the mass effect is centered in the
posterior fossa, cerebellar tissue may herniate both upward
through the tentorial incisura and downward through the
foramen magnum, with compression on the midbrain and
medulla. The CSF secretion persists as long as a cerebral blood
flow is maintained; however, neither the CSF nor the brain
parenchyma is compressible. The main complication of a rapid
increase of ICP is the compression of the subependymal and
cortical veins and engorgement of the intracerebral capillaries
in between. The increased capillary pressure, in turn, increases
the brain swelling and edema, while herniations fill the
tentorial incisura and the foramen magnum, increasing the
pressure even more. The result of the process can only be an
intracranial circulatory arrest when the perfusion pressure
cannot overcome the intracranial pressure. These changes may
occur early in hyperacute hydrocephalus or as a late, terminal
complication of progressive hydrocephalus. On imaging, the
whole parenchyma becomes edematous with loss of gray-white
matter contrast and, if administered, intravenous contrast
would pool in the surface vessels.
Most acute changes of hydrocephalus resolve after treatment,
but some (ependymal damage, gliosis, and abnormal
myelination) may be permanent.[49] On imaging, the most
obvious long-term consequence of hydrocephalus is permanent
ventriculomegaly caused by irreversible degeneration of the
brain tissue, especially in the posterior parts of the hemispheres,
with patent pericerebral spaces. Demyelination and axonal
degeneration result in a similar MR appearance: bright T2/
FLAIR signal usually seen, or seen more, in the paraventricular
white matter associated with brain volume loss. Subependymal
fibrosis and sclerosis are usually found at autopsy;[44] it may
appear in young infants as a hypointense ventricular lining
interposed between the bright CSF and bright periventricular
white matter T2 weighted images.
Imaging of Treated Hydrocephalus and Resulting
Complications
Therapeutic goals and options
In acute or decompensated hydrocephalus, CSF is diverted to
relieve the pressure and restore the brain perfusion; compliance
must also be restored. In chronic hydrocephalus, the treatment
aims primarily at restoring normal compliance. Methods
are ventriculoperitoneal drainage and endoscopic third
ventriculostomy (ETV). Other approaches (diuretics, lumbar,
or ventricular taps) are not much used. Ventriculoperitoneal
shunts (VPS) have been favored for a long time, but they have
limitations: they may become infected, break, or become
obstructed when the choroid plexus “colonizes” the catheter
as the ventricles get smaller. The intracranial segment may
become too short as the head ventricular sizes decrease. The
extracranial segment may also become too short as the child
grows. The peritoneum may fail to absorb the CSF properly,
with the formation of peritoneal cysts. Both under- and over-
drainage may occur. Therefore, shunt revisions are needed all
too often. Morbidity and mortality are not negligible.[53]
 Raybaud and Krishnan: Hydrocephalus in children
Therefore, endoscopic third ventriculostomy (ETV) has become
a significant and popular technique as an alternative to
shunts when the ventricles are obstructed anywhere caudal
to the tuber cinereum. It restores the compliance, and if the
ventricular absorption is poor, diverts the ventricular CSF
toward the peripheral absorption sites
Imaging assessment of ETV and shunts
Assessment of Endoscopic Third Ventriculostomies. MR is the study
of choice for assessing the efficacy of a third ventriculostomy.
It demonstrates the surgical stoma in the tuber cinereum
(millimetric CISS/FIESTA), and the flow-void of the CSF
pulsing through it (sagittal T2 FSE).[54] In children who have
undergone a successful ETV, the reduction in ventricular size
is slower than in those who have been treated using ventricular
shunts:[55] several months, instead of several days as in patients
with ventricular shunt catheters. Even on late follow-ups,
the ventricles remain larger than they would be after shunt
placement.[56] This may be linked to the pressure wave of the
basilar artery pulsating just below the stoma, which also may
explain the upward convexity of the normal tuber cinereum.
The authors of this review, like others, feel that classical
sagittal 3–4-mm T2 FSE is as sensitive as cine phase-contrast
sequences to show the pulsating CSF flow-void through the
stoma[54] [Figure 5].
Radiologic assessment of shunt function. Neuroimaging is
mandatory when a shunt malfunction is suspected. In infants,
this can be done by ultrasonography, at least as a first approach.
In older children, fast CT is still the standard study in many
places, but fast MR imaging can provide a quick assessment of
the ventricular size and the shunt placement, without sedation
and without ionizing radiation; therefore, it is recommended.
As the parenchyma cannot be compressed, ventricles may
remain unchanged in acute presentations while ICP keeps
raising, but the pericerebral spaces are effaced. Occasionally,
significant subependymal fibrosis may prevent the ventricles to
expand. In any case, the clinical expression is more important
than the ventricular size.
The most common cause of malfunction is occlusion of the
ventricular catheter by choroid or glial tissue. Another cause is
Figure 5: ETV. Sagittal midline T2FSE. Prominent flow void across the tuber
cinereum attesting the patency of the stoma.
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S289
a disjunction of the shunt components; if the site (ventricular
versus peritoneal portion) cannot be determined clinically,
plain film studies of shunt components are necessary.
The rate of shunt infection resulting from ventricular shunting
has decreased over the years and is now generally appreciated
at between 1%[56] and 5%–10%, higher in infants.[53,57] Most shunt
infections develop shortly after insertion, but approximately
10% may develop months or years later following a systemic
infection, peritonitis, trauma, or surgery.
Clinically significant subdural collections are uncommon after
shunting, affecting approximately 5% of adult and pediatric
patients.[58] More significant collections may be CSF-like on CT,
CSF-like, or hyper proteinic on MR, or blood containing on both
modalities. For post-traumatic collections, a hygroma could
form first by accumulating interstitial fluid and the secondary
neoangiogenesis could bleed.[59]
Slit ventricle syndrome
In “slit ventricle syndrome,” shunted hydrocephalic patients
present symptoms of a “shunt failure” while the ventricles
and pericerebral spaces are very small on imaging.[61] It is
characterized by a single clinical-radiological pattern but can
be explained by very divergent processes. Di Rocco classified
such patients into three groups:[62] (1) slit ventricle syndrome
with normal ICP: the inability of the ventricles to expand is
due to fibrotic stiffness at the subependymal level; (2) slit
ventricle syndrome with low ICP: overdrainage or siphoning
of CSF through a shunt catheter or a chronic CSF leak; (3) slit
ventricle syndrome with high ICP: craniocerebral disproportion
secondary to an early suture fusion. Thus, shunted patients
with headaches and slit-like ventricles may experience diverse
disorders with totally different treatments. However, it should
be stressed that the morphologic findings of very small
ventricles in shunted patients are not enough to diagnose what
is, above all, a clinical syndrome.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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 Review Article

Access this article online

Quick Response Code:
Hydrocephalus in Low and
Middle‑Income Countries ‑ Progress
and Challenges
Johannes M N Enslin, Nqobile S Thango, Anthony Figaji, Graham A Fieggen
Website:
www.neurologyindia.com

DOI: Abstract:
10.4103/0028-3886.332285
Hydrocephalus remains one of the most commonly treated neurosurgical conditions worldwide. Caring for
patients with hydrocephalus requires infrastructure and political support and initiative; these are often difficult to
obtain in low‑ and middle‑income countries (LMICs). Some innovations that have arisen in LMICs have traveled
up the financial gradient to high‑income countries, such as the combination of endoscopic third ventriculostomy
with choroid plexus coagulation to manage hydrocephalus. The development of neuro‑endoscopy has played
a major role in managing hydrocephalus worldwide; however, LMICs still face specific challenges, such as
limited access to shunt hardware, a disproportionately high incidence of post‑infectious hydrocephalus,
unique microbiological spectra, and often poor access to follow‑up care and neuroimaging. This has received
increased attention since the Lancet Commission on Global Surgery. The goal of improving access to quality
neurosurgical care through various initiatives in LMICs will be discussed in this manuscript. The need for
neurosurgeons continues to grow in LMICs, where better access to neurosurgical care, adequate neurosurgical
training and political support, and patient education are needed to improve the quality of life for patients with
common neurosurgical conditions. Despite these challenges, treating hydrocephalus remains a worthwhile
endeavor for many patients.
Key Words:
Development, hydrocephalus, low‑ and middle‑income countries, management

Key Message:
Hydrocephalus is one of the most common neurosurgical conditions. Low- and middle- income countries
have unique challenges and etiologies to hydrocephalus. These countries offer unique insight and innovation
with a major scientific contribution to the understanding of managing hydrocephalus in children. This review
focuses on this valuable contribution.

A lthough modern neurosurgery has

improved patient survival and outcomes
for many conditions, people living in low‑ and
even though this categorization and definition
is more than 90 years old.[3] Hydrocephalus has
various causes and these may differ, sometimes
middle‑income countries (LMICs) have significantly, based and socioeconomic status
Department of unfortunately seen very little benefit from and geographic locations. [4‑6] A systematic
Surgery, Division this. Many LMICs still have very limited or no review by Isaacs et al.[6] showed that Africa
of Neurosurgery, access to neurosurgical services.[1] In the Lancet has close to a twofold higher prevalence
University of Cape Commission on Global Surgery 2030 report, of pediatric hydrocephalus than North
Town and Red Meara et al. report that approximately two America (104/100,000 vs. 55.6/100,000). There
Cross War Memorial billion people in low‑income countries and rural are also age‑based differences in many countries
Children’s Hospital, areas have limited access to essential surgical where, for example, Asia shows a prevalence
Cape Town, services.[2] of elderly hydrocephalus of 656.9/100,000,
South Africa compared to a prevalence of 52.8/100,000 when
Hydrocephalus is an umbrella term for a group combining North America and Europe.[6]
Address for of pathologies that share the finding of abnormal
correspondence: enlargement of cerebral ventricles. [3] The Untreated hydrocephalus has a high mortality
Dr. Johannes MN Enslin,
condition is categorized into two broad groups, rate of 20%–87%,[7] and caring for patients with
Department of Surgery,
Division of Neurosurgery, namely communicating and noncommunicating,
University of Cape Town How to cite this article: Enslin JM, Thango NS,
and Red Cross War This is an open access journal, and articles are distributed under the terms Figaji A, Fieggen GA. Hydrocephalus in Low and
Memorial Children’s of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 Middle-Income Countries - Progress and Challenges.
Hospital, Cape Town, License, which allows others to remix, tweak, and build upon the work Neurol India 2021;69:S292-7.
South Africa. non‑commercially, as long as appropriate credit is given and the new
creations are licensed under the identical terms. Submitted: 31-Aug-2021 Revised: 23-Oct-2021
E‑mail: johannes.enslin@ Accepted: 25-Oct-2021 Published: 11-Dec-2021
uct.ac.za For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com

S292 © 2021 Neurology India, Neurological Society of India | Published by Wolters Kluwer - Medknow
 Enslin, et al.: Hydrocephalus in LMIC’s
hydrocephalus is a resource‑intensive process that includes
diagnostic work‑up, shunt insertion, endoscopy equipment,
shunt products, follow‑up visits to clinics and hospitals,
regular neuro‑imaging, and managing complications such
as shunt infections, shunt blockages, wound breakdown and
erosions, or complications of over‑drainage. Furthermore, these
children often need special schooling and neurodevelopmental
follow‑up. The cost of caring for in‑patient hydrocephalus
patients in the United States of America alone was estimated
at $2 billion per year in the early 2000s.[8]
The causes of hydrocephalus in developing countries are also
different from the etiology in developed countries, where
post infectious causes are responsible for approximately 60%
of hydrocephalus cases in developing countries in Africa.[9]
If, on top of all the above, one considers that only around 50%
of all shunts are functional after two years of it being placed,[9‑12]
the immense scale of the problem comes into stark reality.
With the burden of disease so heavily swayed toward people
living in LMICs, especially of pediatric hydrocephalus, this
population warrants special attention and strict protocols for
managing and diagnosing hydrocephalus.
Epidemiology
The incidence of hydrocephalus is 123 per 100,000 births in
LMICs compared to 79 per 100,000 births in high‑income
countries.[4] It is also interesting to note that there was no
difference found among countries that routinely fortify with
folate when compared to countries in the same region that do
not fortify with folate.[6]
Hydrocephalus is still one of the most common birth defects
globally, with an estimated 400,000 new cases per year
worldwide.[5] Therefore, surgery for hydrocephalus is one
of the most commonly performed neurosurgical procedures
worldwide.[5] Hydrocephalus is typically a consequence of
other conditions: reportedly approximately 85% of patients
with a posterior fossa tumor present with hydrocephalus and
approximately 30% of them have permanent hydrocephalus
after successful tumor removal[13]; 1% of children with bacterial
meningitis[14] and up to 4% of children who sustain a traumatic
brain injury [15] develop hydrocephalus, whereas 12% of
children with syndromic craniosynostosis and approximately
20%–30% of patients after subarachnoid hemorrhage[16]
develop hydrocephalus. We also know that approximately
80% of children with open spinal dysraphism develop
hydrocephalus.[17] Therefore, it is easy to see that the burden
of disease is weighted toward parts of the world with a lower
socioeconomic status where health care infrastructure may be
lacking, that is, LMICs.
Managing of hydrocephalus in a child with a post fossa tumor
also requires special mention in LMICs. There are often delays
in accessing appropriate preoperative imaging, long transfer
times, and sometimes no surgeon is able to perform definitive
tumor resection.[2] In these cases, managing hydrocephalus
becomes even more important. [18] Avoiding shunting as
the primary intervention is therefore not always possible.
Transferring a child with an external ventricular drain is never
a good idea, and often the definitive tumor surgery can only be
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S293
done at a different unit or in a different country. Endoscopic
third ventriculostomy is a good option in these scenarios,[19]
but often the referring unit does not have facilities or expertise
to do this. In these scenarios, an early ventriculoperitoneal
shunt may be the only option if the child presents with raised
intracranial pressure signs and a delay is anticipated before
definitive surgery. This does carry some risks, such as upward
herniation, uncontrolled reduction of intracranial pressure, and
possible delay in definitive treatment of the tumor.
Compounding factors
The burden of hydrocephalus disease is largest in Africa,
South America, and South‑East Asia.[4] In Africa and India,
there are approximately 6000 new cases of hydrocephalus
born every year; in Eastern Africa, hydrocephalus is by
a long way the most commonly treated neurosurgical
condition.[9] Added to this major burden of disease in LMICs,
there is a discrepancy between the patient numbers and the
availability of trained neurosurgeons. In some countries in
sub‑Saharan Africa, there is a patient to neurosurgeon ratio
of 5–10 million people to 1 neurosurgeon.[9] Fortunately, this
is changing with a steadily increasing number of well‑trained
neurosurgeons in LMICs. In a recent review on the state of
neurosurgery in sub‑Saharan Africa, Karekezi et al. found
on average 1 neurosurgeon to care for 6 million inhabitants
in 2020.[20] In a country like South Africa, there is a ratio
closer to 1 neurosurgeon for every 450,000 people.[5] To put
these numbers into perspective, there was a ratio of 1.47
neurosurgeons per 100,000 population in the United States
of America in 2016.[21] This places an even larger urgency on
training and production of more qualified neurosurgeons at
a rate that still outdoes the current rate.[22]
Delay in presentation to neurosurgical care, and therefore
delay in treating hydrocephalus or conditions that may lead
to hydrocephalus, such as tumors and cerebral infection,
compounds the problem in LMICs. Patients often have to travel
for hours or days to get to the closest primary care facility,
and from there, they need to be referred to a neurosurgical
unit, often another few days’ wait and hours of travel time.
Children with disabilities are still often ostracized in rural
communities in low‑ and middle‑income countries. Various
forms of religious and folklore are still commonly attached
to children with conditions such as hydrocephalus.[23] This
may lead to parental delay in healthcare‑seeking behavior.
It is not uncommon to see children present with massive
macrocrania (more than 100 cm) accompanying open spinal
dysraphism that was allowed to close by secondary granulation
rather than surgery.[5]
Financial support for caring for children with hydrocephalus
and other neurosurgical conditions, in general, is often lacking
in LMICs. Shunts are expensive, sterile facilities may be
expensive, and proper long‑term follow‑up for children with
hydrocephalus costs money. It is not unheard of that patients
can only be operated on and receive a shunt if they can pay
for it out of their own pockets in some countries.[5] Fortunately,
philanthropic donations and a worldwide emphasis on
the global burden of disease that commits governments to
reallocate funds to improve healthcare for all are changing this
scenario, albeit slowly.[24] But there is definitely movement in
the right direction.
 Enslin, et al.: Hydrocephalus in LMIC’s
Local practices
The role of endoscopic techniques in managing hydrocephalus
is well‑established. [25,26] A successful endoscopic third
ventriculostomy may to a great extent obviate the need for any
further procedures, and there is no implanted hardware that can
become infected. When further combined with a procedure that
reduces cerebrospinal fluid production such as choroid plexus
coagulation, it seems that in certain geographical areas this may
improve the outcome of third ventriculostomies even further.[26]
Treating patients with hydrocephalus comes with a commitment
to follow‑up, manage complications such as infection and
blockage of the shunt, and caring for the neurodevelopmental
comorbidities and cognitive impairments that will affect
schooling and employment opportunities. While guidelines
may recommend that hydrocephalus be managed in a particular
evidence‑medicine based manner, the reality for many LMICs
is that not all shunts are inserted by neurosurgeons. In
some countries, hydrocephalus is managed by primary care
practitioners, general surgeons, or even nonmedical personnel
in some instances.[27] There have also been innovative strategies
such as developing locally produced low‑cost shunts, such as
the “Harare‑shunt” and “Malawi‑shunt” in these developing
nations.[28,29] Innovations, such as the Chhabra shunt, have for
many decades been a very effective shunt, available at a low
cost and with a seemingly low complication rate, that is used
throughout countries in Africa and South‑East Asia.[30‑33]
Strategies
Some strategies used to aid in neurosurgical care for patients
with hydrocephalus, among other conditions, are the concept
of surgical camps, where a single surgeon or a small team
travels to a remote location and performs clinics and surgery
on as many individuals as possible in a short period.[1] While
this strategy may work well for an individual patient in
the short term, there are often difficulties with follow‑up,
and managing any complications may be impossible, as the
team leaves again after a short period. Educational activities
in which the local communities are educated on causes and
identification of hydrocephalus, as well as educating young
people and motivating them to become healthcare workers
and surgeons, that can in future improve the local community’s
health care.[1] Training is another focus where neurosurgeons
from LMICs are trained abroad and then return to their own
countries to deliver care. This strategy works very well but it
often happens in LMICs that the neurosurgeon then returns
to a hospital without the necessary support and infrastructure
to allow them to practice at their full potential and capacity.
More emphasis in Africa is currently being placed on training
neurosurgeons for Africa, in Africa, with more specialized
centers providing training to candidates from neighboring
countries, and then once trained, the neurosurgeons go back to
their own country. Often, these neurosurgeons will then start
training local neurosurgeons as well. This works very well and
prepares the neurosurgeon for the environment that he or she
will face once back home.[20] The concepts of “task‑shifting” and
“task‑sharing” are receiving more attention in neurosurgical
literature currently.[34] A further strategy is to focus on the
improvement of the healthcare structure in LMICs.[1] Health
policy and advocacy groups are addressed, and this can go
a long way to improve care of patients in a meaningful and
sustainable way. But this takes time.
S294 Neurology India | Volume 69 | Supplement 2 | November-December 2021
Etiology of hydrocephalus by region
One of the fascinating observations when looking at a global
topic like hydrocephalus is to note the geographical differences
in the etiologies of the condition in LMICs in Africa, South‑East
Asia, and South America versus the rest in Europe and
North America. Congenital causes such as aqueduct stenosis
occur among all people, and better antenatal care including
maternal‑fetal ultrasound scanning leads to earlier detection of
hydrocephalus. This may allow termination of the pregnancy to
be considered. As more premature babies survive in developed
countries, an increase in the incidence of posthemorrhagic
hydrocephalus is seen. In many LMICs, antenatal care may
be inadequate and fetal imaging is seldom available; thus,
termination of pregnancy for medical reasons is not common
practice in most LMICs. In striking contrast, up to 60% of
hydrocephalus in some African centers is post‑infectious in
etiology[35,36] [Figure 1a and b show typical imaging]. Western
countries have a predominant Staphylococcus epidermidis
bacterial burden with shunt infections, while in LMICs, this
may be completely different. In a Kenyan study, it was found
that there is a predominance of gram‑negative organisms.[37]
This needs to be considered in choosing the most appropriate
prophylactic antibiotic. Bacterial infections predominate, but
in Nepal and South American countries, neurocysticercosis
may also cause hydrocephalus.[38] Although the incidence of
neural tube defects is on the decline worldwide, this remains a
problem in most LMICs.[6] Up to 80% of all children with open
neural tube defects are thought to develop hydrocephalus.
Tuberculosis has been eradicated in most developed countries
around the world, while it remains a major concern in LMICs
where most tuberculous meningitis occurs.[39] Many patients
with tuberculous meningitis develop hydrocephalus; this
increase in intracranial pressure, together with the vasculitis
process, is cause for the major disability that these cases
suffer.[40]
Therapeutic options
CSF diversion through insertion of a shunt remains the gold
standard for managing hydrocephalus. There have been
important technological advances in the materials used, valve
a b
Figure 1: (a) T2WMRI of a 3‑month‑old baby with myelomeningocele and
hydrocephalus, complicated by E‑Coli ventriculitis that has resolved. This MRI was
done to plan endoscopic assisted shunt placement and fenestration. (b) CT brain
without contrast in a 7‑month‑old baby with Gram‑negative sepsis and ventriculitis
that caused multiloculated hydrocephalus. This scan was performed prior to the
treatment of hydrocephalus
 Enslin, et al.: Hydrocephalus in LMIC’s
design, and antibiotic impregnation, but this costs money,
limiting penetration into LMICs. However, it seems that
outcomes in patients with hydrocephalus may not depend
solely on the type of material of the shunt, nor the valve
mechanism.[11,31] The Chhabra shunt, as an example of a more
basic shunt, seems equally efficacious when compared to
their more expensive counterparts. The neuro‑endoscope
holds particular promise in managing hydrocephalus in
LMICs.[5] Together with the advantage of not relying on an
implanted device, endoscopic approaches may entail lower
cost, shorter operation time, negligible risk of infection,
and less stigmatization in the communities (for example,
through an externally visible shunt profile).[41,42] This has led
to the enthusiastic uptake of neuro‑endoscopy by colleagues
managing hydrocephalus in resource‑limited settings.[25] The
work done by Warf et al. in Uganda has taken this further in
combining standard endoscopic third ventriculostomy (ETV)
with choroid plexus coagulation (CPC).[25,26] This group also
reported their success in reducing the need to shunt infants with
open neural tube defects in Uganda after combining an ETV
and CPC in this subgroup.[17,43] This has been corroborated by
researchers in high‑income countries, albeit with lower success
rates.[44] A particular challenge in managing hydrocephalus in
LMICs is the higher incidence of multiloculated hydrocephalus,
which demands a great deal of skill and experience.[5] The
skills obtained by regularly performing endoscopy on this
post‑infectious cohort of patients likely aids the surgeons
to have higher success rates than others in their use of the
neuro‑endoscope.[45]
Ultrasound is also a great tool to help with intracranial
navigation through an open fontanelle or even via a small
craniotomy in older patients. Smartphones are also being
employed with specially designed applications to aid in
shunt placement navigation.[46,47] Some older devices, such
as the Ghajar guide, are also still in use in many LMICs with
great success to aid in shunt placement guidance.[47] All of
these techniques are valuable in reducing the morbidity that
is associated with malpositioning of a shunt and resulting in
blockages or failures.[5]
Wound care after surgery for hydrocephalus presents
challenges in many LMICs where access to healthcare facilities
is limited. This has led to innovative wound closure strategies
such as the use of Superglue (a cheap and readily available
general use craft glue) rather than expensive tissue glue to
“seal” the wound after surgery. [5] This works better than
dressings to prevent soiling, and once the glue falls off, the
wound is usually healed, obviating the need to have patients
visit clinics for wound inspections and removal of sutures.
Fetal surgery for myelomeningocele holds the promise of
reducing the need to treat hydrocephalus in these patients,[48,49]
but this is not offered routinely in most countries around
the world, and least of all in LMICs. However, the prospect
is immense; if this intervention does indeed lead to a lower
incidence of hydrocephalus and better outcomes in those who
develop hydrocephalus, the impact will be even greater in
LMICs. Apart from the cost of establishing such a program, the
major concern relates to risk to the mother and an increased
risk of premature labor, and in a resource‑limited setting, this
may be disastrous.[5]
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S295
Follow‑up care
Follow‑up of patients with hydrocephalus requires a life‑long
commitment from the healthcare team. Regular clinic visits
are required to check wounds, shunt tract health, head
circumference (especially in young children), fundoscopy, and
symptom inquiry to detect shunt failure with raised intracranial
pressure, shunt over‑drainage, or infection. Any healthcare
worker can be trained to recognize these signs; thus, it is ideal in
LMICs that these visits are outsourced to non‑neurosurgeons,
but there needs to be a local contact neurosurgeon or clinician
that can manage the complications as soon as possible if
they arise. Telemedicine and virtual consultations have
also aided this process immensely over the past few years,
certainly something that has been underlined by COVID‑19.
Geographical barriers in LMICs, such as mountainous traverses
in Nepal, ocean crossings between Indonesian islands, and
vast desert treks in parts of Africa, South‑East Asia, and South
America, can be overcome by using virtual outreach projects.
Resources can then be pooled to allow physical transfer of only
those patients who are in need of a neurosurgeon.
Most high‑income countries base follow‑up imaging in patients
with hydrocephalus on MRI scanning, which offers exquisite
definition and no radiation exposure. In most LMICs, there is
very limited access, or none at all, to MRI scanning. Computed
tomography (CT scanning) is the mainstay of follow‑up
hydrocephalus patients, which leads to multiple radiation
exposures in many children. The use of ultrasound in children
with an open fontanel has been implemented to very good use
as a valuable tool for clinicians in LMICs.[50,51]
In addition to knowing that the shunt or ETV is working, it is
important to look at the neurodevelopmental and cognitive
milestones in patients with hydrocephalus. It may be
difficult to obtain formal neuropsychological assessment in
LMICs where there are very few pediatric neurologists and
neurodevelopmental specialists. This can be overcome through
collaboration between LMICs and higher‑income country
partners, an excellent example of which is the Boston–Uganda
collaboration of Warf et al. at Mbale.[52,53]
Outcomes
From the studies by Warf, Kulkarni, Constantini, and others,
it appears there may be very little difference in the outcome
of managing hydrocephalus wherever one practices,[54,55,36]
especially when accounting for the variables encountered
in LMICs and the higher rate of complex cases such as
post‑infectious hydrocephalus. An impressive success rate of
70% has been reported from Uganda with ETV in post‑infectious
hydrocephalus patients if cerebral aqueduct stenosis is present,
versus a 45% success rate if the aqueduct is patent.[35] Most of
the prediction tools in use today to determine the success of
an ETV have been developed based on outstanding work done
in LMICs,[56] with the most important predictors of outcomes
reported to be age and head circumference at presentation,
and etiology.[57]
Conclusion
People living in LMICs may encounter many difficulties in
accessing healthcare, but thanks to dedicated neurosurgeons
 Enslin, et al.: Hydrocephalus in LMIC’s
working in these settings, often in partnership with colleagues
from better‑resourced countries, patients with hydrocephalus
are able to receive effective treatment. Clinicians need
to be aware of the differences in aetiologies, pathology,
microbiology, and infrastructure in LMICs, tailoring care to
these factors. Research opportunities abound, leading to a
better understanding of the causes of hydrocephalus in these
settings, and more effective treatment options. Neurosurgeons
in LMICs can stand firm in the knowledge that with proper
planning they do not have to stand back for others when it
comes to offering patients with hydrocephalus the care they
deserve.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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 Review Article

Access this article online

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Website:
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Fetal Ventriculomegaly and
Hydrocephalus – What Shouldn’t be
Missed on Imaging?
Liat Ben Sira1,2,3, Danil A. Kozyrev5, Dafna Ben Bashat2,3,4, Shlomi Constantini2,5,
Jonathan Roth2,5, Shelly I. Shiran1,2

DOI:
10.4103/0028-3886.332286
Abstract:
Fetal ventriculomegaly is one of the most frequently diagnosed abnormalities detected prenatally. The finding
of additional subtle abnormalities can facilitate accurate prognoses, which may range from normal outcomes
to significant neurodevelopmental sequelae. Pathogenesis and imaging patterns of ventriculomegaly and
hydrocephalus in the fetus based on the pattern‑recognition approach using fetal MRI are reviewed in this
paper. This radiological approach may shed light on clinical course prediction and therapeutic efficacy of
hydrocephalus in the fetus.
Key Words:
Congenital hydrocephalus, fetal MRI, hydrocephalus, MRI, ventriculomegaly

Key Messages:
Fetal ventriculomegaly is an entity that can coexist with other brain abnormalities. Identification and
understanding of the pathogenesis of these abnormalities is a key factor for future prognosis. The radiological
approach helps to understand clinical course prediction and therapeutic efficacy of hydrocephalus in the fetus.

1
Division of Pediatric
Radiology, Tel Aviv
F etal ventriculomegaly is one of the most
frequently diagnosed abnormalities of the
fetal central nervous system. The incidence
term “hydrocephalus” describes a subset of
ventriculomegaly patients who also have
increased cerebrospinal fluid (CSF) pressure
Sourasky Medical is approximately 0.3–2.0 cases per 1000 within the ventricular system. Given the challenge
Center, Tel Aviv, pregnancies.[1,2] It is defined as in utero enlargement of making this distinction prenatally, the term
2
Sackler Faculty of of the lateral ventricles and is considered a finding “hydrocephalus” is typically reserved for fetuses
Medicine, Tel Aviv that may be the “tip of the iceberg” due to high with a more severe degree of ventriculomegaly,
University, Tel Aviv, association with other anomalies. Thus, the obvious site of obstruction, effacement of the
3
Sagol School of finding of ventriculomegaly in the fetal brain subarachnoid space, or enlarged head size.[3]
Neuroscience, Tel Aviv should prompt a thorough investigation of
University, Tel Aviv, the entire brain and body in the fetus, which is It is important to establish correctly the accurate
4
Sagol Brain Institute, crucial for counseling parents. Based on accurate diagnosis of ventriculomegaly—defined as
Tel Aviv Sourasky diagnosis, the prognoses may range from normal enlargement of the ventricular atria of more
Medical Center, Tel outcomes to significant neurodevelopmental than 10 mm throughout pregnancy. Ultrasound
Aviv, 5Department of sequelae, shedding light on clinical course is the initial imaging study in pregnancy used to
Pediatric Neurosurgery, prediction and therapeutic efficacy, including evaluate fetal anatomy.
Dana Children’s the timing and success of surgical treatment.
Hospital, Tel Aviv In the following review, we will discuss the The sonographic evaluation of lateral ventricular
Medical Center, Tel definition and pathogenesis of ventriculomegaly size, specifically the atria, is performed in the
Aviv, Israel and hydrocephalus in the fetus, their imaging axial plane, in the trans ventricular plane at the
appearance, and the pattern‑recognition approach level of the glomus of the choroid plexus, and
Address for on MRI evaluation to facilitate accurate diagnosis. perpendicular to the ventricular cavity, with
correspondence:
the positioning of the calipers inside the echoes
Dr. Liat Ben Sira,
Division of Pediatric Ventriculomegaly is the preferred term for generated by the lateral walls.[4‑6]
Radiology, Department enlarged ventricles identified in utero. The
of Radiology, Dana How to cite this article: Sira LB, Kozyrev DA,
Children’s Hospital, Tel This is an open access journal, and articles are distributed under the terms Bashat DB, Constantini S, Roth J, Shiran SI. Fetal
Aviv Medical Center, of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 Ventriculomegaly and Hydrocephalus – What Shouldn't
6 Weizmann Street, License, which allows others to remix, tweak, and build upon the work be Missed on Imaging? Neurol India 2021;69:S298-304.
Tel Aviv 64239, Israel. non‑commercially, as long as appropriate credit is given and the new
creations are licensed under the identical terms. Submitted: 01‑Sep‑2021 Revised: 05‑Oct‑2021
E‑mail: bensiraliat@gmail. Accepted: 11‑Oct‑2021 Published: 11-Dec-2021
com For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com

S298 © 2021 Neurology India, Neurological Society of India | Published by Wolters Kluwer - Medknow
 Ben Sira, et al.: Imaging in fetal hydrocephalus
The severity of ventriculomegaly is based on standardized
strict criteria derived from the width of the atrium of the lateral
ventricle, subclassified into mild (10–12 mm), moderate (12–
15 mm), and severe (>15 mm).
US is limited by the ability to penetrate the fetal calvarium and
by technique quality as it is operator‑dependent; thus, fetal MRI
has emerged as a valuable tool to complement ultrasonography
findings in ventriculomegaly. Fetal MRI has superior contrast
resolution, making it the study of choice in the evaluation
of fetal neuroanatomy.[7-9] MRI has several advantages such
as providing true three‑dimensional information with high
spatial resolution and multiple contrasts that indirectly detect
microstructural properties of the tissue. Therefore, MRI can
characterize subtle intracranial findings, such as migration
disorders, hemorrhage, parenchymal destruction, and tissue
integrity and white matter fibers organization,[5,10] which can
be difficult to detect on ultrasound and tend to have a later
presentation during pregnancy. Common fetal MRI brain
protocol mainly includes T2‑weighted images to demonstrate
brain structure and anomalies, with the addition of T1‑weighted,
balanced steady‑state free‑precession, diffusion‑weighted
imaging, and spectroscopy to detect ischemia and tissue
integrity. Recent studies using state‑of‑the‑art machine
learning methods have demonstrated the ability to quantify
the volume of the ventricles and CSF rather than just using
2D measurements.[10,11]
In cases of seemingly isolated ventriculomegaly detected by the
prenatal US in which no additional anomalies were identified,
fetal MRI has been shown to detect additional abnormalities
in 20%–50% of cases.[12] Higher quality US may lower this
difference as shown in more recent studies.[13,14] While the
prenatal US is operator‑dependent, fetal MRI is also heavily
dependent on the interpretation expertise.
In cases of isolated mild‑moderate ventriculomegaly, the
incidence of abnormal development is 0%–8%. Assuming
the diagnosis is confirmed on a high‑quality fetal MRI,
isolated ventriculomegaly portends a good prognosis
for the neurodevelopmental outcome. It is agreed that
severe ventriculomegaly (hydrocephalus) carries a bad
prognosis. Approximately four out of five fetuses with
an antenatal diagnosis of apparently isolated severe
ventriculomegaly (>15 mm) survive. There is a high (3/5)
chance of neurodevelopmental delay in this group.[15]
Although fetal ventriculomegaly can progress to postnatal
hydrocephalus, it can also be due to acquired or intrinsically
decreased cerebral volume in the absence of intracranial
hypertension; differentiating between these two entities may
be challenging.
The pathophysiology of fetal hydrocephalus is not well
understood. A major obstacle to advancing our knowledge
of the causes of this disorder and the cellular responses that
accompany it is the multifactorial nature of hydrocephalus.
The epidemiology is varied and complex, and the injury
mechanisms are numerous and overlapping. The age of onset
strongly influences the degree of impairment, especially in
the developing brain. Injury severity is dependent on the
magnitude and duration of ventriculomegaly. The primary
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S299
targets are periventricular axons, myelin, and microvessels.
Cerebrovascular injury mechanisms are prominent; gliosis and
neuroinflammation play a major role.[16]
The traditional concept that hydrocephalus is the result of an
imbalance between the production and absorption of CSF,
also known as the bulk flow theory, has been challenged,
especially with regard to communicating hydrocephalus, with
studies demonstrating routes of CSF absorption in capillaries
and not only arachnoid granulations, as once believed.[17] The
understanding of “minor pathway hydrocephalus” in the
immature brain and differentiating it from the conventional
classification of obstructive and nonobstructive “major
pathway hydrocephalus” helps in diagnosis and treatment
strategy.[18]
The consensus classification of hydrocephalus recently
proposed reflects the surgical approach to hydrocephalus,
which is to divert the CSF between the site of production and
the location of the obstruction based on the concept of points
of restriction of flow.[19]
This classification relates to resistance to outflow or obstruction
in five anatomic locations within the central nervous system.
The potential locations of restriction are the foramina of Monro,
the aqueduct of Sylvius, the out‑flow foramina of the fourth
ventricle, the flow from the spinal subarachnoid space (SAS) to
the supratentorial SAS, and the terminal absorptive site where
CSF empties into the systemic circulation.[20]
Radiological Evaluation of Fetal Ventriculomegaly
and Hydrocephalus
A systematic approach to fetal MRI evaluation is thus
crucial. The search pattern should include, but not be limited
to, evaluation of the ventricular morphology, ependyma,
caudothalamic notch, corpus callosum, septum pellucidum,
posterior fossa, parenchymal signal and sulcation, head size,
and extracranial findings.
In this review, instead of describing a list of the various
etiologies related to fetal hydrocephalus, we would like to
present a diagnostic approach to the radiological systematic
analysis of ventriculomegaly based on scrutinizing anatomical
structures followed by recognizing pathophysiological
mechanisms based on Guibaud and Lacalm.[4]
Ventricular anatomy and CSF flow
Workup of ventriculomegaly should include a complete
analysis of the ventricular system, from the supratentorial
ventricles to the infracerebellar cisterns. Pathologies generating
ventriculomegaly between the diencephalon and posterior
fossa, including the aqueduct of Sylvius at the level of the
mesencephalon, are often overlooked. Scrutinization of the
third ventricle, the thalami, the aqueduct, and the posterior
fossa is crucial, especially in the case of an obstructive pattern
associated with severe ventriculomegaly in the early second
trimester. In such a setting, partial atresia of the third ventricle
with upstream dilatation of the ventricular system associated
with partial fusion of the thalami leads to a diagnosis of
diencephalosynapsis [Figure 1].
 Ben Sira, et al.: Imaging in fetal hydrocephalus
Figure 1: Prenatal and postnatal severe hydrocephalus diagnosed in late
gestation. Upper row: Sagittal and axial T2‑weighted imaging fetal MR performed
at 34 gestational weeks, with enlarged head circumference, dilated supratentorial
ventricles with effacement of extra‑axial fluid, aqueductal stenosis, revealing
abnormal vermis, and mild kinking of the cervicomedullary junction. The
interthalamic adhesion (white arrows) is enlarged and ventrally located. Bottom
row: Sagittal and axial T2‑weighted imaging performed at 2 days of life (born 35
gestational weeks) confirming abnormal kinked—brainstem, hypoplastic vermis,
deep ventral cleft, and butterfly appearance of the brainstem. Interthalamic
adhesion is enlarged and ventrally located (white arrow), as well as severe
supratentorial hydrocephalus
Both diencephalosynapsis and aqueductal stenosis can
be isolated or combined with posterior fossa anomalies,
including cerebellar hypoplasia and rhombencephalosynapsis.
Rhombencephalosynapsis (midline fusion of the cerebellar
hemispheres without a vermis) is observed in up to 27% of cases
of severe hydrocephalus in the fetus.[21] Up to 65% of patients
with rhombencephalosynapsis have coexisting aqueductal
stenosis. Its association with aqueductal stenosis has been
described in a large fetopathologic series.[22]
Another important pathologic finding, ependymal denudation,
is a characteristic feature in fetal hydrocephalus, which affects
the progenitor cells of the subventricular zone. This is believed
to result in the development of subependymal nodules/
heterotopia.[17] Only systematic evaluation of the ventricular
wall, particularly in the parasagittal plane, may suggest the
diagnosis of subependymal heterotopia, presenting as nodular
bulging irregularities of the ventricular wall [Figure 2].
Obstructive pattern
An obstructive pattern refers to ventriculomegaly related
to blockage of CSF flow, either intrinsic or extrinsic to
the ventricular system, regardless of the cause of the
obstruction (e.g., malformative, tumoral, or vascular
origin).[5] Identifying an obstructive pattern is important for
prenatal counseling because the severity of the prognosis is
S300 Neurology India | Volume 69 | Supplement 2 | November-December 2021
related more to the cause of obstruction than to the severity
of ventricular dilatation. The cause of obstruction is not
always apparent; thus, it is important to recognize that the
pathophysiological mechanism of the ventricular dilatation
is obstructive. This pattern includes four parameters:
increased cephalic biometry (head circumference), partial
or complete (barotraumatic) destruction of the cavum septi
pellucidi (CSP), a decrease of pericerebral spaces, and, in some
cases, if the obstruction is downstream of the third ventricle,
presence of a dilated supra‑pineal recess (SPR).[23] In cases of
long‑term and major obstruction of CSF flow in the fetus, a
focally dehiscent cerebral mantle can be an additional finding
to suggest an obstructive pattern.[21]
There are three distinct settings in which not all four
components of the obstructive pattern are present:
• cases of early obstruction
• cases with partial obstruction
• cases evaluated at onset of the obstructive process.
Normal or even decreased cephalic biometry may be
encountered in early obstructive ventriculomegaly in the first
or early second trimester by ultrasound as an early increase
in pressure in the ventricular system may damage progenitor
cells in the periventricular germinal matrix, leading to a
slowing‑down of cephalic growth. Moreover, both decrease in
size of peri cerebral spaces and barotraumatic destruction of
the leaflets of the CSP require a significant increase of pressure
in the ventricular system, accounting for the fact that these
findings may be absent in the early stages of the obstructive
process.
Aqueductal stenosis is the classic example of the supratentorial
pattern of obstructive ventriculomegaly, often moderate to
severe in degree (i.e., hydrocephalus). It might be secondary
to prior hemorrhage or infection, with resultant webs or
gliotic tissue effacing the cerebral aqueduct, sometimes
seen in isolation. Radiological findings include enlarged
third ventricular recesses, aqueduct funneling, and findings
suggestive of previous blood products in the cerebral aqueduct.
The fourth ventricle is typically normal in size.
Although often sporadic, imaging can provide clues to
the diagnosis of several possible genetic and syndromic
associations [Figure 3]. X‑linked hydrocephalus is an important
genetic hydrocephalus syndrome caused by a mutation of the
L1CAM gene on the X chromosome (Xq28). L1CAM‑associated
hydrocephalus is the most common heritable form of
ventriculomegaly with a prevalence of approximately 1:30,000
live births. It is thought to account for up to 10% of males
with isolated idiopathic hydrocephalus,[24] particularly in the
presence of adducted thumbs. L1CAM gene has been linked
to several neurological phenotypes with or without congenital
hydrocephalus (L1 syndrome). L1CAM codes for a neural cell
adhesion molecule transmembrane glycoprotein and, as such,
is essential to nervous system development, including neuronal
migration and differentiation. L1 syndrome with X‑linked
hydrocephalus is usually characterized by bi‑ or triventricular
dilation, aqueductal stenosis, enlarged quadrigeminal
plate, interthalamic adhesion hypertrophy, and vermian
hypoplasia with or without associated kinked brainstem and
diencephalic‑mesencephalic junction dysplasia [Figure 4].[25]
 Ben Sira, et al.: Imaging in fetal hydrocephalus

Figure 2: Severe syndromic hydrocephalus with ciliopathy (CRB2 gene). Sagittal and axial T2‑weighted imaging demonstrating destruction of the cavum septi
pellucidi (CSP), decreased pericerebral spaces with multiple small subependymal nodules (arrowheads) lining the ventricular surface consistent with periventricular nodular
heterotopias (PVNH)

c
Figure 3: Familial genetic NF1A gene mutation with ventriculomegaly. (a) Fetus at 33 gestational weeks: axial and sagittal T2‑weighted imaging. Colpocephaly with abnormal
rounded frontal horns (arrows), abnormal sulcation pattern with wide‑open Sylvian fissure (abnormal operculization), thick septal leaves, thin posterior Corpus callosum
suggesting malformative brain pattern. (b) Same patient, aged 1 year: Axial and sagittal T1, coronal T2‑weighted imaging. Follow‑up with mild dilatation of the ventricles,
abnormal gyration, hypoplastic Corpus callosum confirmed genetic analysis‑Exom NF1A gene (maternally inherited). (c) Axial and sagittal T1, coronal T2‑weighted imaging.
Mother of the patient from a and b with a similar pattern of dysmorphic colpocephaly (dilated occipital horns), abnormal thick fornices, hypoplastic Corpus callosum,
suspected dysgyria, and mental retardation

Neurology India | Volume 69 | Supplement 2 | November-December 2021 S301

 Ben Sira, et al.: Imaging in fetal hydrocephalus

Vascular clastic pattern intraventricular hemorrhage, ventricle wall irregularities,

Underlying “clastic” vascular pathologies such as clots within the ventricles, focal destruction, and liquification
ischemic‑hemorrhagic insults have a typical pattern of in the periventricular parenchyma. Systematic use of T2*
unilateral/asymmetrical ventriculomegaly with gradient echo and SWI MR sequences help prove hemosiderin
intraventricular hemorrhage [Figure 5].

Ventriculomegaly can also occur due to ex‑vacuo enlargement

of the ventricles, secondary to brain destruction, in mechanisms
other than ischemia. These include infection, an inborn error
of metabolism, etc.[3] Insults can be diffuse or focal, sometimes
pattern‑specific, offering insight into the underlying etiology.

Infectious clastic patterns related to infectious fetopathy,

especially cytomegalovirus (CMV), have typically associated
findings: periventricular or parenchymal T2‑weighted
hyperintensities or calcifications, germinolysis cysts, and
pathognomonic cystic changes in the occipital horns or
anterior to the temporal horns [Figure 6]. This pattern can
be associated with an abnormal Sylvian fissure suggestive
of abnormal operculization and polymicrogyria. In the vast
majority of cases, they are associated with mild or moderate
ventriculomegaly, which can easily be considered as “isolated”
ventriculomegaly if this infectious clastic injury is missed.
Involvement of the parenchyma due to CMV infection carries
a poor prognosis when associated with a decrease in cephalic
biometry, cortical insult, or hypoplasia of the cerebellum.

Perinatal stroke encompasses a group of heterogeneous

Figure 4: Congenital severe hydrocephalus with suspected diencephalic–
mesencephalic Junction dysplasia. Sagittal T2‑weighted imaging with multiple level
axial T2 demonstrating butterfly‑like appearance of the midbrain with a deep ventral
cleft, as well as severe supratentorial ventriculomegaly. Additional unexplained T2
hyperintense lesion in the medulla
conditions in which a focal disruption of cerebral blood
flow secondary to arterial or cerebral venous thrombosis
or embolization often results in a pattern‑specific injury.
Periventricular venous infarction is part of the spectrum of
germinal matrix and intraventricular hemorrhage and may
occur in utero. It is thought to be caused by the obstruction

a b c d

e f
Figure 5: Periventricular hemorrhagic infarction and intraventricular hemorrhage. Fetus at 28 gestational weeks with irregular borders of asymmetric ventricular dilatation,
lined by hyperintense T1 and DWI‑weighted imaging (b and c) signal consistent with blood products (arrows) as confirmed on T2* susceptibility sequence (d). T2
(a and e and f) show focal dilatation of the ventricles with liquification of the adjacent parenchyma and evolution of focal porencephalic cysts, consistent with grade IV
hemorrhage periventricular hemorrhagic infarction (PVHI)

S302 Neurology India | Volume 69 | Supplement 2 | November-December 2021

 Ben Sira, et al.: Imaging in fetal hydrocephalus
Figure 6: Cytomegalovirus (CMV) prenatal infection of the brain. Upper row – axial
and coronal; lower row – sagittal T2‑weighted imaging. Fetus at 34 gestational
weeks referred due to ventriculomegaly, demonstrating CMV infectious pattern with
germinolysis cysts, periventricular hyperintense T2 diffuse signal abnormality in the
deep white matter, and typical cystic changes (arrows) posterior to the occipital and
anterior to the temporal horns
of the medullary and terminal veins by the associated
intraventricular hemorrhage, resulting in venous congestion,
ischemia, and hemorrhagic infarction.[26] Imaging in the acute
stage demonstrates a germinal matrix hemorrhage with
parenchymal extension [Figure 5]. Diffusion‑weighted imaging
reveals a rind of cytotoxic edema. In the chronic phase, there
is an evolution of blood products and development of focal
cystic encephalomalacia of the periventricular white matter,
termed “caudal triangle,” that is often lined by residual blood
products. The underlying ventricle is enlarged and may
be associated with retrograde neuronal degeneration and
disrupted migration.[3]
Conclusion
Fetal ventriculomegaly is the most common CNS abnormality
found in the fetus. Imaging has an important role in the
workup, facilitating prognostication and counseling of future
parents.
While the presence of additional anomalies increases the risk of
neurologic sequelae, the severity is dependent upon the nature
of the additional anomalies. In this review, we elucidate the
anatomical and etiological diagnostic tools for the analysis of
ventriculomegaly and hydrocephalus, helping guide families
and providers in the planning of pregnancy and postnatal care
in fetuses with ventriculomegaly.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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11. Gholipour A, Akhondi‑Asl A, Estroff JA, Warfield SK. Multi‑atlas
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12. Griffiths PD, Brackley K, Bradburn M, Connolly DJA,
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14. Di Mascio D, Sileo FG, Khalil A, Rizzo G, Persico N, Brunelli R,
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15. Carta S, Kaelin Agten A, Belcaro C, Bhide A. Outcome of fetuses
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S304 Neurology India | Volume 69 | Supplement 2 | November-December 2021

 Review Article

Access this article online

Quick Response Code:
Prenatal Ventriculomegaly – Diagnosis,
Prognostication and Management
Vivek Krishnan, Akshatha Sharma1, Rachita Ramamurthy2, Rinshi Elayedatt,
B S Ramamurthy2

Website:
www.neurologyindia.com
Abstract:
DOI: Fetal ventriculomegaly (VM) refers to the abnormal enlargement of one or more ventricles of the brain in‑utero.
10.4103/0028-3886.332280 The enlargement may or may not be related to ventricular obstruction and increased intracranial pressure;
therefore, the term “hydrocephalus” is not used. VM is diagnosed usually in the mid‑trimester when the atrial
diameter (AD) of the lateral ventricle is more than 10 mm on one or both sides. A thorough workup is then
required to identify the cause as the etiology is diverse. Fetal magnetic resonance imaging (MRI) may yield
additional information. Serial ultrasound follow‑up would be required to assess its progression with advancing
gestation. The prognosis and long‑term outcomes greatly depend upon the etiology, the severity at diagnosis,
progression, and associations. This article reviews the definitions, diagnosis, and workup of fetal VM, discusses
follow‑up protocols and prognosis, and examines the role of fetal therapy, including fetoscopic surgery in its
prenatal management.
Key Words:
Counselling, fetal ventriculomegaly, prenatal diagnosis, prognosis

Key Messages:
Fetal ventriculomegaly (VM) refers to the abnormal enlargement of one or more ventricles of the brain in‑utero.
VM is diagnosed usually around mid‑trimester when the atrial diameter (AD) of the lateral ventricle is more
than 10 mm. A thorough workup is then required to identify the cause from its diverse etiologies and other
structural or genetic associations. Serial ultrasound follow‑up would be required to assess its progression with
advancing gestation. The prognosis and long‑term outcomes greatly depend upon the etiology, the severity
at diagnosis, and its progression as well as its associations.

F etal ventriculomegaly (VM) refers to the

Fetal Medicine and
Perinatology, Amrita
Centre of Excellence
in Fetal Care, AMRITA
Institute of Medical
Sciences, Kochi,
Kerala, 1Apollo Centre
for Fetal Medicine,
Indraprastha Apollo
Hospitals, New Delhi,
2
Srinivasa Ultrasound
Scanning Centre,
Bangalore, Karnataka,
India
Address for
correspondence:
Dr. Vivek Krishnan,
Fetal Medicine
and Perinatology,
AMRITA Institute of
Medical Sciences,
Kochi, Kerala, India.
E‑mail: drvivekkrishnan@
gmail.com
enlargement of one or more of the ventricles
of the fetal brain, as identified by prenatal
ultrasound (US).[1] Lateral ventriculomegaly
may be unilateral or bilateral; bilateral
ventriculomegaly with third ventricular
dilatation is termed triventricular dilatation,
and if the fourth ventricle (4V) is dilated, the
term “quadri‑ventricular dilatation” is used. It
is one of the most common fetal findings seen
in the mid‑trimester anomaly scan and has a
birth prevalence of 0.3–1.5 per 1000 live births
in different series. This number could be an
underestimation as most studies are based
on clinical assessment at birth and fetal VM
is presumably asymptomatic at birth in most
cases.[2] The term “hydrocephalus” refers to a
pathological increase in intracranial cerebrospinal
fluid (CSF) volume and pressure usually
associated with altered CSF hemodynamics.[3] It
is generally a clinical rather than a US diagnosis.
This is an open access journal, and articles are distributed under the terms
of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0
License, which allows others to remix, tweak, and build upon the work
non‑commercially, as long as appropriate credit is given and the new
creations are licensed under the identical terms.
For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com
The term, although often used synonymously
with VM, should not ideally be used in the
prenatal context as ventricular pressures cannot
be measured by prenatal US. Moreover, while
hydrocephalus implies VM, the latter can also
result from loss of brain tissue or atrophy of
the brain (ex vacuo phenomenon) and in some
malformations of cortical development such
as lissencephaly, where there is no increase in
intracranial pressure.[4]
VM is a finding with diverse etiology, varying
severity, and a wide range of neurodevelopmental
outcomes. In this article, we review the definitions,
diagnosis, and workup of fetal VM. We then
discuss follow‑up protocols and prognosis of VM
as it relates to parental counseling and predicting
postnatal outcomes. Finally, we examine the role
of fetal therapy, including fetoscopic surgery in
the prenatal management of fetal VM.
How to cite this article: Krishnan V, Sharma A,
Ramamurthy R, Elayedatt R, Ramamurthy BS. Prenatal
Ventriculomegaly – Diagnosis, Prognostication and
Management. Neurol India 2021;69:S305-12.
Submitted: 24‑Jul‑2021 Revised: 08-Nov-2021
Accepted: 10-Nov-2021 Published: 11-Dec-2021

© 2021 Neurology India, Neurological Society of India | Published by Wolters Kluwer - Medknow S305
 Krishnan, et al.: Fetal ventriculomegaly – diagnosis, management
Definitions
VM is defined based on the diameter of the lateral ventricles
at the atria—the junction of the body, temporal, and occipital
horns. The atrium is characterized by the presence of the
glomus of the choroid plexus, which is highly echogenic,
while the occipital horn is filled with cerebrospinal fluid. The
mean values of the atrial diameter (AD) range from 6.2 ± 1
to 7.6 ± 0.6 mm and is known to remain constant during the
second and third trimesters.[5] Therefore, a value of 10 mm
is three to four standard deviations above the mean, and
any value that exceeds this defines ventriculomegaly at any
gestational age.[6] Although this cut‑off was determined several
years ago, it remains valid even with more modern equipment,
particularly at mid‑gestation.
VM can be further classified into mild‑moderate fetal
VM (MVM), when the AD is 10–15 mm), and severe VM, when
the AD is >15 mm5. Other groups refer to an AD of 10–12 mm
as mild and 12.1–15 mm as moderate VM.[6‑12] The rationale
for this classification is that the risk of associated anomalies
and abnormal neurodevelopmental outcomes are higher with
increasing severity. However, considerable heterogeneity in
clinical behavior is observed in children with the same degree
of ventricular dilatation.[6]
The term “isolated VM” is used when the lateral ventricular
dilatation is not accompanied by other abnormal intracranial
or extracranial findings or genetic syndromes. VM may also
be classified as transient, stable, or progressive based on the
evolution.
“Symmetric VM” refers to bilateral dilatation with a difference
in AD <2 mm while “asymmetric VM” implies either unilateral
VM with a normal contralateral ventricle or bilateral VM with
a difference of ≥2 mm in AD.
Diagnosis
A diagnosis of fetal ventriculomegaly is made by US
measurement of the AD. While oblique/incorrect measurements
of AD can increase the false positivity of VM,[8] if measured
properly, it is the single most sensitive indicator of a fetal
central nervous system (CNS) anomaly, with a sensitivity of
88%.[9] Table 1 enumerates the factors that make AD the chosen
measurement in the diagnosis of VM.[10]
The atrial diameter (AD) at any gestation is measured in the
trans‑ventricular plane with a symmetric appearance of the
cerebral hemispheres. The measurement is taken with the
glomus of the choroid plexus in view as this defines the atrium.
The parieto‑occipital fissure serves as an anatomic landmark
for this measurement. The calipers are positioned at the inner
margins of the proximal and distal walls of the lateral ventricles,
with the measurement being taken perpendicular to the long
axis of the lateral ventricle[4] [Figure 1].
Although a screening examination of the fetal CNS warrants
measuring only the ventricle farther from the probe[12] (“far
ventricle”), AD of both lateral ventricles should be measured,
particularly if the ventricle closer to the probe (“near ventricle”)
looks dilated on eye‑balling. Measurement of the AD of the
S306 Neurology India | Volume 69 | Supplement 2 | November-December 2021
Table 1: Favorable attributes that support the
diagnostic use of AD
First area to dilate in fetal VM
Dilates to a greater extent than any other region of the LV
Lacks constriction from the striatum in comparison to anterior
portions of the LV
AD remains constant between 20 and 40 weeks of gestation.
Its walls are perpendicular to US beam in the trans‑ventricular plane
Measurement has low intra and interobserver variability
Low false‑positivity for AD >10 mm
a
b
Figure 1: (a) Fetal central nervous system screening examination in a 20-week
fetus in the trans-ventricular plane (TV) showing the cavum septi pellucidi (CSP),
comma-shaped frontal horns, lateral sulcus (LS), and posterior horns of both lateral
ventricles, choroid plexus (CP), and parieto-occipital sulcus (POS). (b) The correct
plane in which the atrial diameter (AD) is measured, with the parieto-occipital
fissure serving as a landmark
near ventricle is obtained in a true axial image with intracranial
symmetry on either side of the midline. Symmetry of the brain
should not be assumed lest unilateral VM of the near ventricle
be missed. Visualization of the near ventricle is achievable
by the angled technique[5]—positioning the transducer more
caudally (posteriorly) on the fetal head and angulating it
cephalad (anteriorly) so that the calvarium is scanned through
the lambdoid suture or the thinner squamous portion of the
temporal bone [Figure 2].
Etiology
The etiology of fetal ventriculomegaly is quite varied, from
normal physiological variation to structural or genetic disorders
associated with serious impairment. Mild ventriculomegaly
is likely to represent a normal variant if no other structural
abnormalities (intracranial or extracranial) are noted and
if chromosomal abnormalities and infections are ruled out.
However, it is not possible to determine the truly isolated nature
of ventriculomegaly with certainty during pregnancy; therefore,
a normal variant is a diagnosis of exclusion that cannot be made
until after birth. The likelihood of ventriculomegaly being a
normal variant decreases with increasing degrees of dilation.
The causes of fetal VM can broadly be classified into obstructive
and nonobstructive causes. These have been listed in Table 2.
The latter can in turn be related to CSF hypersecretion,
abnormalities in brain development, or ex vacuo dilatation due
to loss of cerebral cortex.
 Krishnan, et al.: Fetal ventriculomegaly – diagnosis, management

delays should raise suspicion of a familial cause and a

geneticist’s consultation should be sought.[13] Hydrocephalus
occurring in males points to an X‑linked recessive condition
due to L1 cell adhesion molecule (L1CAM) mutation. History
of previous fetal or neonatal intraventricular hemorrhage may
direct the investigation toward fetal neonatal alloimmune
thrombocytopenia (FNAIT) where corrective strategies can be
initiated early in subsequent pregnancies.[14]

History of maternal medical disorders such as uncontrolled

Figure 2: The angled technique of visualizing the ventricle proximal to the probe.
diabetes, intake of teratogenic antiepileptics, or any other drug
The transducer is swung in an arc across the mother’s abdomen and angled to intake should be elicited as these can cause neural tube defects.
visualize the near ventricle through the lambdoid suture or the thinner squamous
portion of the temporal bone A history of fever with rashes, exposure to preschoolers, pets
at home, gardening, intake of uncooked meat, or a history of
Table 2: Etiology of fetal VM travel to endemic areas (e.g., Zika virus) must be documented
Mechanism Conditions associated along with the gestational age at possible exposure.[13] Typically,
Obstruction to CSF Aqueductal stenosis
if transmitted, viral/protozoal fetal infections in the first/early
outflow second trimester cause maximum injury to the growing brain.
Intraventricular hemorrhage, infection, and
fibrosis Knowledge of whether the illness occurred at a vulnerable
Intracranial tumors and cysts gestational age is useful in clinical correlation/counseling.
Chiari‑II malformation
Maternal TORCH IgG, IgM, and IgG avidity can identify the
chronology of infections if any.
Dandy‑Walker malformation
CSF Hypersecretion Choroid plexus papilloma
Extended neurosonogram
Developmental Agenesis of corpus callosum
A detailed neurosonogram (NSG) entails multiplanar scanning
disorders of the brain Holoprosencephaly
of the fetal brain much like an MRI. The diagnosis of VM
Malformations of cortical development
necessitates a detailed neurosonogram.[15] The routine axial
Brainstem dysgenesis including planes  (transventricular and transcerebellar) are used for
rhombencephalosynapsis
screening and diagnosis of VM. In addition to the posterior
Loss/destruction of Hypoxia‑ischemia
horns of the lateral ventricles, the anterior complex (cavum
cerebral cortex and Metabolic causes
ex‑vacuo dilatation septum pellucidum, the frontal horns, genu of corpus callosum,
Infections (CMV, Toxoplasma, Zika virus) interhemispheric fissure, callosal sulci), the parieto‑occipital
As part of genetic Down syndrome sulci, and the Sylvian fissure are evaluated. The coronal
syndromes Walker‑Warburg syndrome planes (transfrontal, transcaudate, transthalamic, and
Bardet‑Biedl syndrome transcerebellar planes [Figure 3] enable the display of both
Meckel syndrome lateral ventricles across the midline, periventricular regions,
Joubert syndrome CSP, corpus callosum, third ventricle, and the cerebellum.
Hydrolethalus syndromes
The midsagittal planes [Figure 4] evaluate the corpus callosum,
third ventricle, midbrain, pons, aqueduct, fourth ventricle, and
The most common cause of fetal VM is aqueductal stenosis and
the vermis. The parasagittal “three horn view” [Figure 5] gives
is noted in 20%–30%.[4] Although VM is a component of several
a panoramic view of the lateral ventricles in their entirety and
genetic syndromes, there are relatively few genetic causes of
is extremely useful to look at the ventricular walls and the
isolated ventriculomegaly. Syndromes typically associated
periventricular region. A specialist experienced at scanning the
with ventriculomegaly as well as additional abnormalities
fetal brain understands the evolution in sulcations at different
that can be identified sonographically or by fetal magnetic
gestations and these are evaluated specifically every time the
resonance imaging (MRI) include Down syndrome, Walker– fetal brain is reviewed in all the above planes for progression
Warburg, Bardet–Biedl, Meckel, Joubert, and hydrolethalus or regression of VM. A targeted scan of the spine should be
syndromes. undertaken in all cases of fetal VM, especially when the head
signs—Lemon and Banana signs—are noted as they may be
Workup subtle or occult [Figure 6]. Lastly, a thorough extracranial
assessment should be performed to rule out infection markers
As discussed above, VM is a finding and has myriad causes. such as hepatosplenomegaly, ascites, intra‑abdominal
A detailed workup is essential to reach the final diagnosis so as calcifications, as well as other structural anomalies as VM is a
to aid in counseling and management. The following evaluation part of several genetic syndromes and associations have been
protocol is suggested. reported in up to 76% of cases.[16‑18] In a meta‑analysis by Pagani
et al.,[19] approximately one‑third of the apparently structurally
History isolated mild ventriculomegalies had additional anomalies
History of consanguinity, previous pregnancy, or child with on a detailed workup. Approximately 7.4% had additional
malformation (CNS or otherwise) or neurodevelopmental abnormalities on postnatal imaging.
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S307
 Krishnan, et al.: Fetal ventriculomegaly – diagnosis, management

a b c
Figure 3: (a) Normal trans-caudate view, (b) Absent CSP with “steer horn” frontal horns (solid arrowheads) (c) Absent septum pellucidum

a b c
Figure 4: (a) Normal mid-sagittal view, (b) Agenesis of corpus callosum, (c) Vein of Galen malformation (solid arrowhead) with dilated straight sinus

a b c
Figure 5: (a) Normal para-sagittal view, (b) Three horn view in obstructive hydrocephalus, (c) calcifications (stars), periventricular cysts (arrowhead), periventricular halo in
CMV infection (arrows)

Genetic workup Role of MRI

The risk of Trisomy 21 increases by a likelihood ratio of 3.8
when a structurally isolated VM is diagnosed.[20] The presence
of associated prenatal ultrasound findings increases the risk
of abnormal karyotyping from 3% to 8%.[19] Further, 10%–15%
have an abnormal finding on microarray.[13] This incremental
yield has now led to the offering of chromosomal microarray as
the first line of testing. The presence of associated abnormalities
rather than the severity of VM is associated with an increased
incidence of pathogenic copy number variations (CNVs).[21]
History of consanguinity/recurrent CNS malformations would
require exome sequencing in addition to microarray testing for
chromosomes and CNVs.
Thus, amniocentesis is strongly recommended for microarray
and TORCH PCR (even if there is no maternal history
suggestive of infection) on the amniotic fluid in all cases.
The utility of MRI depends on the effort and expertise that
have gone into the ultrasound performed. The additional
yield of MRI after a detailed NSG is 5% as compared to 16%
over standard axial planes.[22] Clinically relevant information
on MRI after a detailed transvaginal neurosonogram is
1.5%.[23] If facilities for an extended neurosonogram are not
available, MRI should be availed provided the radiologist is
conversant with the fetal brain and its anomalies. MRI has an
advantage in diagnosing cortical/migration abnormalities,
callosal abnormalities, and small hemorrhagic foci and is
not impeded by calvarial shadowing, maternal obesity, or
fetal position.[9] The additional information from an MRI
examination may modify the diagnosis and hence the
prognosis and counseling. The Society of Maternal‑Fetal
Medicine suggests offering MRI after 22–24 weeks where
available [Figure 7].[13]

S308 Neurology India | Volume 69 | Supplement 2 | November-December 2021

 Krishnan, et al.: Fetal ventriculomegaly – diagnosis, management
a b
d e
Figure 6: A 32-week fetus with bilateral severe ventriculomegaly with midline disruption (a and b). Extended neurosonogram revealed the “lemon” and “banana” signs
(c and d). Subsequent evaluation of the fetal spine showed a myelocele beginning at the L4 lumbar vertebra (e and f)
Follow‑up
Optimal timing and frequency of follow‑up ultrasound
examinations depend on the ventricular size and gestational
age at diagnosis as well as other factors such as the cause and
associated findings.[13]
For example, if VM is first identified in the mid‑trimester
anomaly scan (around 20 weeks of gestation) as is most often
the case, a follow‑up study at 26 weeks is essential to assess the
cortical sulcation. If VM is identified earlier than 18–20 weeks of
gestation, a repeat scan at 21–22 weeks is necessary to evaluate
the corpus callosal development.
Generally, beyond 26 weeks, a 3 to 4‑week interval between the
ultrasound examinations is ideal to monitor the ventricular size
and any other associated findings such as sequelae of infection.
The ventriculomegaly (especially mild VM) can regress (return
to normal size), remain stable, or progress. The trend of the VM
helps in prognostication.
Severe VM may warrant closer monitoring, especially towards
term, in order to evaluate progression and cranial size which
in turn may dictate the mode of delivery.
Prognosis
Prognosis of fetal VM is usually studied in terms of survival
and neurological outcome after birth. The most important
factors determining these are the severity of the VM and the
association with other structural or genetic abnormalities.
In truly isolated VM, the outcome significantly correlates
with ventricular dilatation. [19] Antenatally undiagnosed
abnormalities are more frequent in the group showing
progressive enlargement of the ventricles as compared to the
ones that remain stable or regress.[24] Various groups have tried
to extrapolate antenatal findings to predict postnatal outcomes.
These groups believe that while the conventional ventricular
AD measurement acts as a screening test, morphologic and
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S309
c
f
volumetric evaluation of these ventricles from stored 3D
datasets using virtual organ computer‑aided analysis (VOCAL)
method and MRI help in prognostication and prediction of
postnatal outcomes. Ventricular morphology evaluation gives
important information on the etiology of VM, supporting
prognosis prediction, and the decision‑making process.[25] An
atrial diameter of >20 mm has a high correlation with the need
for postnatal shunt (>75% require postnatal shunting).[26]
Mild to Moderate Ventriculomegaly (MVM)
The survival rates for fetuses with mild or moderate VM
were reported as 98% and 80%, respectively.[17] Overall, more
than 90% of the fetuses with isolated mild VM and 75%–93%
of the fetuses with isolated moderate dilatation have normal
neurodevelopmental outcomes.[13,27] The subgroup of fetuses
with isolated unilateral VM apparently have better outcomes
than when the dilatation is bilateral. A meta‑analysis by Scala
et al. showed that the prevalence of abnormal neurodevelopment
was 5.9% in fetuses with apparently isolated, unilateral
MVM (atrial width <15 mm) and 7% in fetuses with truly
isolated, unilateral VM. Similarly, the prevalence of associated
CNS abnormalities was significantly higher in symmetric VM
compared with asymmetric VM (38.8% vs. 24.2%, respectively,
for all CNS abnormalities and 20% vs. 7.1%, respectively, for
major CNS abnormalities).[28] Progressive ventriculomegaly
is seen in 14%–16% of MVM cases and these have a poorer
outcome.[29] 57% of MVM cases are stable, while in 29%,
regression occurs with good outcomes.[24]
Severe Ventriculomegaly (SVM)
Most cases of SVM are associated with neural and extracranial
anomalies and the prognosis is generally poor, with a reported
survival of 33%.[17] Early‑onset and progressive SVM also has a
poor neurodevelopmental outcome. Cases of SVM with genetic
and chromosomal etiologies such as X‑linked hydrocephalus
carry the worst prognosis and have severe neurodevelopmental
deficits and a short life span.[30,31]
 Krishnan, et al.: Fetal ventriculomegaly – diagnosis, management

a b c
Figure 7: Prenatal MRI of the fetal brain at 32 weeks shows bilateral severe ventriculomegaly (a). Retro cerebellar cystic structure with mass effect on the cerebellar
hemispheres and the fourth ventricle with resultant ventriculomegaly, likely representing an arachnoid cyst, in the same fetus as in a. (b). Bilateral ventriculomegaly in a 30
weeks’ fetus that shows nonvisualization of cortical sulci and a smooth cortical surface suggesting Lissencephaly Type 1 (c)

Most cases of SVM (especially progressive SVM) require high (procedure‑related death of 17%).[39] Based on this data, a
postnatal surgery (to relieve intracranial tension) and regular moratorium was issued in 1985 on further in‑utero procedures
monitoring and therapy. for fetal VM.

Approximately one‑third of the cases of severe ventriculomegaly Between 1999 and 2007, two independent studies[3,40] looked
survived without disability. Further, 9.5% had additional at VA shunting by the hysterotomy route. In both studies, the
abnormalities detected postnatally, none of which was without outcomes were poor, with infection and sepsis being major
disability.[32] complications, despite technical success of the procedures.

Counseling Modern proponents of the VA shunt point out several

Depending on the grade of fetal VM and gestational age, the
expectant couple must be counseled regarding investigations
required, follow‑up, prognosis, postnatal treatment; or option
of pregnancy termination (for cases of poor prognosis) by a
multidisciplinary team involving the obstetrician, geneticist,
neurodevelopmental specialist, and pediatric neurosurgeon.
It is also important to counsel the couple on recurrence risk in
subsequent pregnancies. Recurrence risk is determined by the
cause of VM. X‑linked hydrocephalus carries a 50% recurrence
risk in male fetuses. Autosomal recessive syndromes carry a
recurrence risk of 25%. SVM of other causes carries an empirical
recurrence risk of 4%.[33]
Fetal Surgery
Early animal studies on the feasibility of CSF diversion in fetal
VM had shown significant clinical improvement in fetuses
that underwent the same as compared to controls.[34‑37] Despite
several limitations of these studies, favorable preliminary
data on the outcomes led to human trials, the rationale being
that CSF diversion at an early stage in utero would relieve
intracranial pressure and normalize cerebral blood flow,
thereby preventing irreversible brain damage.[38] Initial human
trials involved multiple cephalocentesis, but this was soon
replaced by percutaneous ventriculo‑amniotic shunting as
the latter minimized the need for repeated interventions and
its cumulative complications. This method gained acceptance
in due course, and with the establishment of an international
registry of fetal surgery by the International Society of Fetal
Medicine and Surgery in 1982, 39 such procedures were
reported in three years. An analysis of these reports suggested
that the results were not promising (53% had serious and
12% had mild to moderate neurological morbidity despite
intervention) and the complications were unacceptably
reasons for the suboptimal outcomes associated with these
early attempts. Poor understanding of the etiopathological
mechanisms of VM and thereby improper patient selection,
inferior quality of ultrasound machines, nonavailability of
fetal MRI, lack of new generation genetic studies such as
whole‑exome sequencing, and less refined surgical techniques
were some of these.[41‑43]
Most of these deficiencies have been circumvented in current
fetal care, leading to a renewed interest in VA shunting,
particularly by the percutaneous route. In addition, the shunt
equipment has also greatly been improved with anchoring
mechanisms to prevent shunt migration, kink‑resistant
tubes, and one‑way valves to prevent amniotic fluid from
entering the ventricles and causing ventriculitis. [39,44,45]
Nevertheless, patient selection would be a crucial factor
for the successful implementation of in‑utero VA shunting.
Selecting fetuses with pathologies most likely to benefit from
a procedure such as isolated aqueductal stenosis, which would
increase the likelihood of a favorable outcome. An ongoing
prospective study of the North American Fetal Therapy
Network (NAFTNet) is looking at the performance of US
vs. MRI in accurately identifying the cohort of patients with
isolated AS.[38] Similarly, fetuses with severe, progressive VM
and thinning of the cortical mantle before 28 weeks gestation
are believed to be better candidates as irreversible damage
could occur in such cases beyond 32 weeks. Involvement of a
multidisciplinary team that includes fetal medicine specialists,
obstetricians, pediatric neurosurgeons, neonatologists,
pediatric surgeons, and fetal anesthetists is an essential
prerequisite for centers that plan fetal therapeutic VA shunting.
However, the lack of a proper randomized trial addressing
the effectiveness of VA shunting over postnatal management
leaves this procedure as an investigational one at present, until
at least more robust evidence is available.

S310 Neurology India | Volume 69 | Supplement 2 | November-December 2021

 Krishnan, et al.: Fetal ventriculomegaly – diagnosis, management
Conclusion
Fetal VM, defined as in utero enlargement of one or more
of the cerebral ventricles, is a finding and not a diagnosis.
The etiology is protean with varied neurological outcomes.
VM can be isolated or associated, stable or progressive,
and of varying severity. Associated anomalies, progressive
dilatation, and increasing severity adversely affect the overall
outcome. A comprehensive workup including extended
neurosonogram, MRI, and tests for genetic disorders and
infection and serial follow‑up can lead to a specific diagnosis,
better prognostication, and improved patient counseling. Fetal
therapy by VA shunting remains investigational at present
for want of robust evidence. However, with advances in fetal
diagnosis and treatment, there is renewed interest in the area
and further studies and prospective trials are expected to give
a clear answer in the near future.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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 Review Article

Access this article online

Quick Response Code:
Management of Posthemorrhagic
Hydrocephalus
Naren Nayak, Suresh K Sankhla

Website: Abstract:
www.neurologyindia.com
Background: Although there are several successful treatment options available today, the optimal management
DOI: of posthemorrhagic hydrocephalus (PHH) still remains undetermined.
10.4103/0028-3886.332257 Objective: To evaluate the efficacy and outcomes of contemporary treatment methods and to define current
evidence‑based management for PHH in premature infants.
Material and Methods: Literature was reviewed to identify and analyze merits and demerits of the currently
available temporizing measures and definitive treatment for premature low‑birth weight babies with PHH.
Results and Conclusions: Advances in treatment and increased experience have led to redefinition of
treatment goals to optimize cognitive neurodevelopment, and quality of life in these premature infants with
PHH. Current literature favors early diagnosis and intervention using temporizing measures, and prevention
of future complications of PHH with a permanent CSF diversion method such as ventricular shunting or
endoscopic third ventriculostomy.
Key Words:
Germinal matrix hemorrhage, intraventricular hemorrhage, posthemorrhagic ventricular dilatation, premature,
temporizing measures

Key Message:
Based on recent literature, the management of PHH is focused mainly on early surgical intervention with the
aim to clear intraventricular blood and its breakdown products to reduce cognitive disability, the incidence of
multiloculated hydrocephalus, and the need for permanent shunt placement.

G erminal matrix hemorrhage, intraventricular

Department of
Neurosurgery, Global
Hospital, Parel,
Mumbai, Maharashtra,
India
Address for
correspondence:
Dr. Suresh K. Sankhla,
Room No. 112, 1st Floor
OPD, Global Hospital,
35, Dr. E. Borges Road,
Parel, Mumbai – 400 012,
Maharashtra, India.
E‑mail: sankhlasuresh@
gmail.com
hemorrhage (IVH), and posthemorrhagic
ventricular dilation (PHVD) are complications
of prematurity that may result in cognitive
delay, behavioral abnormalities, epilepsy, visual
impairment, cerebral palsy, and symptomatic
hydrocephalus.[1‑3] Approximately 25%–30% of
premature or low birth weight (LBW) infants
suffer from IVH and a higher incidence is
associated with lower gestational ages and birth
weights.[4] Infants weighing less than 1500 g at
birth are at a higher risk of developing IVH,
and >40% of infants with birth weight 500–750 g
are likely to suffer IVH.[5,6] It has been estimated
that approximately 25%–50% of neonates with
IVH continue to develop PHVD, and nearly
40% of them require some form of treatment for
hydrocephalus.[7‑11]
The management for IVH and its sequelae
in premature infants has evolved over past
several decades. Although several treatment
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non‑commercially, as long as appropriate credit is given and the new
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paradigms have been proposed, there has been
no clear consensus on the optimal treatment
for PHH and the guidelines or evidence‑based
recommendations are lacking till date. [12‑14]
Presently available therapeutic measures include
diuretics, serial lumbar punctures, ventricular
access devices (VAD), external ventricular
drainage (EVD), and ventriculosubgaleal
shunts (VSGS), as well as the permanent
cerebrospinal fluid (CSF) diversion methods
such as ventriculoperitoneal (VP) shunts and
endoscopic third ventriculostomy (ETV). In
this report, we review the literature to evaluate
the efficacy and outcomes of various treatment
modalities available today and make an attempt to
outline the current evidence‑based management
of prematurity‑related PHVD/PHH.
Diagnosis
Most cases of IVH in premature infants are
diagnosed on cranial ultrasound (USG) which is
How to cite this article: Nayak N, Sankhla SK.
Management of Posthemorrhagic Hydrocephalus.
Neurol India 2021;69:S313-9.
Submitted: 17‑Jun‑2021 Revised: 15-Oct-2021
Accepted: 18-Oct-2021 Published: 11-Dec-2021

© 2021 Neurology India, Neurological Society of India | Published by Wolters Kluwer - Medknow S313
 Nayak and Sankhla: Posthemorrhagic hydrocephalus
performed soon after the birth, either as a routine procedure or
following clinical/systemic instability. There are established
criteria to estimate severity and protocols for serial USG in
preterm LBW babies with IVH/PHVD [15,16] [Table 1]. The
highest risk for bleeding is within the first 48  h after birth
and most IVH is diagnosed by day 7.[17,18] Therefore, a close
surveillance in the first week after birth with cranial USG of
infants with lower gestational age and LBW is extremely crucial
for early diagnosis and successful treatment.
Clinical presentation
1. Clinically Silent: On most occasions, IVH may be clinically
silent and is detected only on ultrasound studies. For this
reason, many authors recommend routine head USG in
any infant born at less than 34 weeks’ gestation or has birth
weight <1500 g.
2. Catastrophic: A rapid neurological deterioration may
occur over a period of minutes to hours mimicking large
intracranial hemorrhage. The clinical signs suggestive of
IVH may include a sudden alteration in vital signs like
bradycardia or apnea, and/or neonatal seizures. A bulging
fontanelle, separation of the sutures, or a rapidly increasing
head circumference may suggest the development of acute
hydrocephalus.
3. Saltatory: Symptoms may evolve over a period of
hours and days with a fluctuating pattern of decreased
alertness, sluggish motor activity, hypotonia, abnormal
eye movements, and respiratory difficulties. Clinical
evaluation for increasing head circumference, fullness of
fontanelle, enlarged scalp veins, and splaying of sutures can
be used to assess progressive ventricular dilatation. Other
more serious clinical signs of raised Intracranial Pressure
(ICP) such as apnea, bradycardia, lethargy, and decreased
activity warn urgent neurosurgical intervention.
Management of IVH and PHH
Management of IVH and posthemorrhagic ventriculomegaly in
premature infants still remains a challenge to clinicians.[12‑14] The
approach to treatment is guided by multiple ongoing factors
mainly responsible for primary brain injury and subsequent
neurodevelopmental outcomes. Brain damage initially caused
by the germinal matrix (GM) hemorrhage is compounded by
the toxic effects of the blood and its degradation products,
especially iron and free radicals. Additional injury is inflicted
by an inflammatory response generated secondary to the
release of proinflammatory cytokines. The development of
hydrocephalus and raised ICP further worsens the insult to
the developing neonatal brain.[17,18] The overall management
of IVH/PHH should thus include aggressive removal
of intraventricular blood and its breakdown products,
and appropriate treatment for raised ICP due to PHVD/
PHH [Table 2]. Currently, there is no consistently proven role of
medical management in patients with PHH. A large multicenter
randomized controlled trial on acetazolamide and furosemide
failed to show any significant benefit in survival or reduction
in the need for shunt surgery when used for posthemorrhagic
ventricular dilatation.[19] It is also clear from the literature that
an early definitive treatment like VPS is mostly unsuitable in
LBW premature infants with PHVD/PHH due to extreme
fragility and immunological immaturity, and is frequently
associated with high risks of anesthetic and surgical morbidity
and increased rates of shunt failure.[20,21] Current management
S314 Neurology India | Volume 69 | Supplement 2 | November-December 2021
paradigm favors the use of temporizing measures initially
during the neonatal period to tide over the crisis in the acute
phase until placement of a permanent ventricular shunt is
considered necessary and safe.[21,22] This regimen has by far
been the most logical therapeutic option in the management
of IVH/PHVD and provides an opportunity to enhance the
neurodevelopmental outcome in infants by reducing the
complications during treatment, to prevent further progression
of hydrocephalus, and to reduce the rates of shunt dependency
and shunt revisions.
Temporizing measures
Commonly used temporizing measures for PHVD/PHH include
lumbar punctures (LP), transfontanelle ventricular puncture (VP),
EVD, VAD, and VSGS [Tables 2‑4]. The choice of temporizing
method, however, remains a matter of debate. Meta‑analysis
of trials from 1980s and 1990s has demonstrated that lumbar
punctures and ventricular taps do not reduce permanent shunt
dependence or neurological disability.[23] Lumbar puncture is
often difficult to perform in clinically unstable infants and its
effectiveness tends to reduce on repeated attempts. Ventricular
tapping is associated with infection, seizures, and parenchymal
injury in the form of hemorrhages and porencephalic cyst
formation. EVD is generally not considered as the first choice
of treatment for PHH because of the associated higher risk of
infection, frequent catheter obstruction, CSF over‑drainage,
subdural hygroma, hyponatremia, and issues related to the
integrity of scalp including wound dehiscence, skin erosion, and
CSF leakage.[24,25] Infants with EVD also require management in
the intensive care until the drain is removed or converted to a
permanent shunt. VAD partly avoids these limitations and is a
good alternative to an EVD.[26] However, VADs are associated
with higher risk of infection due to repeated percutaneous
tappings and cause fluctuations in intraventricular pressure
between very high and very low. The VSG shunts are believed to
provide an alternative method for continuous drainage of CSF in
the treatment of PHH‑related raised ICP. VSGSs have very low
infection rate (6%–8%) and other complications like CSF leakage,
meningitis, electrolyte imbalance, shunt malfunction, migration
of the catheter, and intraparenchymal hemorrhage are rare.[25‑30]
Permanent shunt placement is usually required in 60%–85% of
cases.[25] The main advantage of VSGS, however, is the shorter
hospital stay and the ease with which the patient can be managed
by the nursing and medical staff in the outpatient setting.
Tables 2‑4 summarize comparative results of temporizing
measures in IVH/PHVD. In a systematic review and
meta‑analysis of outcome and complications, Badhiwala
and colleagues,[13] demonstrated no significant difference in
outcome among VAD, EVD, and VSGS. When factors like risks
of infection, rates of permanent VPS placement, and subsequent
shunt revisions are compared, both VADs and VSGSs are
found to be almost equal in effectiveness.[31,32] Frassanito et al.[30]
in a recent publication described a treatment algorithm of
combined neuroendoscopic ventricular lavage (NEL) and VSGS
in 63 infants with PHH and suggested that the combination
is effective and the complication risks including infection and
multiloculated hydrocephalus can be reduced significantly.
Timing of intervention is very crucial and several landmark
studies in recent years have highlighted the importance
of early surgical treatment in premature infants with
 Nayak and Sankhla: Posthemorrhagic hydrocephalus

Table 1: Grading of IVH

Grade Papile’s grading system (CT scan findings) Volpe’s grading system (Echosonographic findings)
Grade I Subependymal hemorrhage Hemorrhage confined to the subependymal GM
Grade II Intraventricular hemorrhage without dilation Hemorrhage within the lateral ventricle without ventricular dilation and/or
hemorrhage occupying less than 50% of the ventricle
Grade III Intraventricular hemorrhage with ventricular dilation Hemorrhage with distention resulting in ventricular dilation and/or
hemorrhage occupying more than 50% of the ventricle
Grade IV Intraventricular hemorrhage with parenchymal hemorrhagePVHI: ventricular hemorrhage that extends into the surrounding parenchyma

Table 2: Treatment options in premature infants with IVH/PHH

Procedure Infection OR/ Need of a Ventricular Sampling Recommendations and Level Comments
rate NICU surgeon dilatation of CSF
Diuretic therapy ‑ NICU No 51% ‑ Not recommended to decrease the Increased risk of morbidity and poor
risk of shunt placement or control neuro‑developmental outcome.
progression of PHH. Level I Nephrocalcinosis reported in 24%
LP 9% NICU No 62% + Not recommended to decrease the No more than three LP for control of
risk of shunt placement or control increased intracranial pressure
progression of PHH. Level I
Ventricular 9% NICU Yes 62% + Not recommended to decrease the 60% porencephalic cyst.Procedure
puncture risk of shunt placement or control is reserved in cases where VP shunt
progression of PHH placement is contraindicated for
urgency, OR is inaccessible, CSF
infection
VAD 15‑22% OR Yes 69‑88% + Treatment option in the CSF removal and sampling as
management of PHH Level II needed; direct administration of
antibiotics
EVD 5.4%‑40%NICU/ Yes 64%‑78% + Treatment option in the Infection rates are lower due to
OR management of PHH better protocols
Intraventricular 16% NICU Yes 60% ‑ Not recommended to decrease the
fibrinolytic agents risk of shunt placement or control
progression of PHH Level I
DRIFT 10% OR Yes 28%‑72% + Not recommended to decrease the Risk of a secondary hemorrhage
risk of shunt placement or control
progression of PHH Level I
VSGS 8%‑16% NICU/ Yes 60%‑86% + Treatment option in the Highly cost effective in hospitals
OR management of PHH Level II lacking resources
Ventricular lavage 4.3% OR Yes 58%‑60% ‑ Not enough evidence to recommend‑
VP shunt 5%‑33% OR Yes 100% ‑ Only definite treatment There is insufficient evidence to
recommend a specific optimal timing
of VP shunt conversion (weight and
CSF protein concentration)
Third ‑ OR Yes ‑ ‑ Insufficient evidence Level III ‑
Ventri‑culostomy
LP, lumbar puncture; VSG, ventriculosubgaleal; EVD, external ventricular drainage; VAD, ventricular access device; VP, ventriculoperitoneal; DRIFT, drainage,
irrigation, and fibrinolytic therapy; NICU, neonatal intensive care unit; OR, operating room; PHH, posthemorrhagic hydrocephalus

PHVD. [33‑36] A retrospective comparative study between
Dutch and Canadian cohorts found lower rates of
cognitive (P = 0.002) and motor (P = 0.03) disability in a
cohort whose treatment was initiated when the VI exceeded
the 97th centile compared to a cohort whose treatment was
initiated in the presence of clinical signs of raised ICP.[34]
The early versus late ventricular intervention study (ELVIS)
has demonstrated that early intervention (VI exceeding
97 th centile or Anterior Horn Width (AHW) >6 mm) is
associated with lesser disability than late intervention (VI
exceeding 97th centile + 4 mm or AHW 10 mm), and the
composite rate of death or disability at 24 months’ corrected
age was 51% in the late intervention group and 35% in the
early intervention group. [35,36] Regardless of the type of
temporizing method used, a close monitoring with regular
head circumference measurement, clinical evaluation, and
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S315
USG assessment is extremely essential to ensure ventricular
dilatation is under control.
Intraventricular blood and breakdown products
The toxic effects of blood and its degradation products on
the developing brain are well documented.[37‑39] It is therefore
not uncommon to see infants whose PHVD has been treated
adequately with an appropriate intervention are still suffering
from serious neurological disability and even infants with less
severe IVH (grades I and II) tend to develop severe neurological
deficits, disproportionate to their initial hemorrhage.[36‑40] Thus,
there appears a role of early removal of the intraventricular
blood and its breakdown products in the management
of IVH/PHVD of prematurity. Use of intraventricular
fibrinolytic agents has been proposed in the past for the
treatment of PHH.[41,42] However, most of the studies using
 Nayak and Sankhla: Posthemorrhagic hydrocephalus

Table 3: Studies showing results in patients with PHH treated by VSGS and NEL
Authors Years Procedure No. of PHH Mean body Mean gestational Infections Mean Mortality Shunt
cases weight (g) age (wks) (%) duration (%) dependency (%)
Sklar et al.[61] 1992 VSGS 62 1560 29.8 10 ‑ 11 89.1
Rahman et al.[27] 1995 VSGS 15 1284 29 0 9.2 wks 0 80
Karas et al.[62] 2007 VSGS 17 ‑ 26 0 56.1 days 0 70.6
Lam et al.[28] 2009 VSGS 16 998 27.4 6.3 ‑ 12.5 71.4
Limbrick et al.[7] 2010 VSGS 30 ‑ 31.7 3.3 20 wks 13.3 76.9
Koksal et al.[25] 2010 VSGS 25 1342 29.3 8 44 day 28 83.3
Nagy et al.[63] 2013 VSGS 72 1037 27.3 8.3 87.9 4.2 100
Ellenbogen et al.[64] 2016 VSGS 22 ‑ 27 9 ‑ ‑ 73
Etus et al.[49] 2018 VSGS 22 <1500 ‑ 36.6 ‑ ‑ 77.2
Schulz et al., 2014 NEL 19 1036 27.8 0 ‑ 0 58
Etus et al.[49] 2018 NEL 23 <1500 ‑ 4.3 ‑ ‑ 60.8
D’Arcangues et al.[47] 2018 NEL 56 1523 31.3 3.6 ‑ 5.4 58.5
Tirado‑caballero et al.[48] 2020NEL 46 1671.86 30.04 21.7 ‑ 6.5 58.7
Frassanito et al.[30] 2021 VSGS + NEL 63 1200 27.8 7.9 32.2 7.9 87.9

Table 4: Comparative results of temporizing measures used in premature infants with IVH/PHH
Factors External ventricular drain Ventricular access device Ventriculo‑subgaleal shunt Neuro endoscopic lavage
Obstruction 6.8% 7.3% 9.6% ‑
Infection 6.7% 9.5% 9.2% 3.6%
Arrest of hydrocephalus 31.8% 17.5% 13.9% 43.4%
Mortality 19.1% 15.3% 12.1% 5.4%
Good ND outcome 56.1% 50.1% 58.7% ‑
Operative revision 47.3% 10.8% 12.2% 8.6%

various intraventricular agents, including recombinant tissue
plasminogen activator (rtPA), streptokinase, and urokinase
have failed to prove effectiveness in the treatment of IVH.[21]
DRIFT Trial
The drainage, irrigation, and fibrinolytic therapy  (DRIFT) is
so far the best study to provide direct evidence in favor of
removal of blood from the ventricles to improve outcome.[43]
The aim of the trial was to decrease mortality and cognitive,
motor, and sensory disabilities. The procedure involves
continuous ventricular irrigation for 72 h to allow clearance of
blood and its products from the CSF. The trial was suspended
prematurely because of suspected treatment futility and
increased risk of secondary bleeding. The short‑term outcomes
from this randomized controlled trial showed no reduction
in shunt surgery or death in the DRIFT intervention arm. In
the long‑term follow‑up, however, the study demonstrated a
significant reduction in the proportion of children with severe
cognitive disability or death at 2 years in the DRIFT arm, from
71% to 54%, and the mean cognitive quotient score was 69.3 in
the DRIFT group and 53.7 in the standard treatment group.[44]
This benefit was maintained at 10‑year follow‑up.[45] The DRIFT
is not recommended for the treatment of PHH because of its
resource‑intensive nature and the risk of secondary hemorrhage,
but it sparked a number of research efforts and opportunities to
investigate optimal treatment approaches for PHH.
Neuroendoscopic Ventricular Lavage
The hypothesis of NEL was based on the 2‑year outcome
results of DRIFT trial which showed a lower morbidity and
reduced cognitive disability in survivors.[44] The technique
involves the use of a neuroendoscope to gently irrigate the
ventricular cavity, remove the blood clots from both lateral
ventricles through a septostomy, ensure patency of the
foramina of Monro, and control bleeding sites under direct
visualization [Figure 1]. Unlike the technique used in DRIFT,
NEL allows for a complete control of inflow, outflow, and
intracranial volume balance in a sterile operative setting.
Infusion of thrombolytic or other agents which may increase
risk of complications is avoided. The procedure is short and
associated with reduced risks of infection and fluctuations in
CSF pressure.
There is no class I evidence of its efficacy but retrospective
evaluations have shown encouraging results regarding
the procedure safety, reductions in VentriculoPeritoneal
Shunt (VPS) insertion and revision rates, and favorable
neurodevelopment outcome.[46‑50] Schulz et al.[51] reported a
significant reduction in the rates of shunt placement (from
100% to 58%), infection, shunt occlusion, and multiloculated
hydrocephalus in the NEL group. There also appears a trend
in their series toward a longer period of shunt‑free interval
in the NEL group compared with the conventional treatment
group. This is important because by the time the shunt
insertion is required, the CSF characteristics and the patient’s
age, weight, and general condition improve in favor of a safe
shunt surgery. However, the majority of these studies have
potential limitations, including the design of the studies,
small patient sample, and no systematic assessment of the
neurodevelopmental outcomes, and hence warrant validation
in an appropriately structured prospective randomized
trial.[49]

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 Nayak and Sankhla: Posthemorrhagic hydrocephalus

a b c
Figure 1: Endoscopic view of the right lateral ventricle during neuroendoscopic lavage in a patient who had developed intraventricular hemorrhage and posthemorrhagic
hydrocephalus. (a) Heavily blood‑stained CSF and unclear view of the intraventricular structures in the beginning of the procedure; (b) Clearer vision and a better view of
the ventricular anatomy after continuous fluid irrigation and aspiration of the blood clots; (c) More clear view of the ventricle and the site of a septostomy. Abbreviations:
CP ‑ choroid plexus, F ‑ fornix, FM ‑ foramen Monro, S ‑ septostomy, SP ‑ septum pellucidum

Permanent CSF diversion
Once temporizing measure is used, a close monitoring with
regular head circumference measurement as well as periodic
clinical and USG assessments is followed to ensure control of
PHVD. A careful evaluation at or around term‑equivalent age
or when the bodyweight is 1.8–2.0 kg is essential to determine
the ongoing need for the temporizing measures and/or to
consider permanent CSF diversion in the form of a VPS/ETV.
Additional data can be obtained from CSF sampling (protein
levels <1.5 g/L, normal cytology, and negative cultures) and
brain imaging with MRI. In recent large series of PHH in
premature infants, the VPS placement rates have been reported
to vary from 58%–100%.[7,20,22,50,52,53]
in this population and a ventriculo‑atrial shunt can be offered
as an alternative, if the diameter of the jugular vein is adequate.
ETV with or without choroid plexus coagulation offers an
alternative to a shunt in the treatment of PHH, as it provides
an opportunity to avoid shunt dependency.[58‑60] However,
with a success rate of 37%–40% and limited data available on
its efficacy in PHH, ETV can only be advocated in selected
patients in whom imaging shows favorable findings like
aqueductal stenosis and triventricular hydrocephalus or a
patent, nonscarred prepontine cistern.
Conclusions

One of many challenges with permanent shunt insertion in
premature infants with PHH is infection, which occurs in
13.8% of cases.[52,54] The high rate of infection in this population
is mainly due to an immature immune system and/or an
inherent impaired inflammatory response.[55] Also, the thin and
fragile skin of LBW infants is vulnerable to frequent wound
breaks and ulcerations over the shunt valve and tubing. Thus,
delaying the procedure until the infant is grown older is likely
to reduce the risk of shunt infection and other complications
significantly. Most authors agree that the following must be
present for a VP shunt to function in a premature infant with
PHH: a mature immune system, an adequate capacity of the
peritoneal cavity, the effective elimination of blood products
from the CSF, and sufficient thickness of subcutaneous tissue.
Recent literature suggests that shunt failure can occur in up to
12.6% of cases within the first 3 months of VP shunt placement
and about 45% of shunts in preterm PHH require shunt revision
within 9 months.[52,54] With regards to shunt infection, results
with the currently available silver or antibiotic impregnated
catheters are promising and the recent British Antibiotic and
Silver Impregnated Catheters for ventriculoperitoneal (Shunts)
BASIC study has demonstrated a 3‑fold reduction in shunt
infection using antibiotic impregnated catheters compared to
standard or silver impregnated catheters.[56] There is no clear
consensus on the optimal valve type to use in these premature
infants. Many authors advocate the use of programmable valves
to avoid potential over drainage and complications like subdural
hygroma or slit‑ventricular syndrome.[57] Peritoneal complications
of VP shunts like bowel perforation, necrotizing enterocolitis,
pseudocyst formation, and malabsorption of CSF are also common
The management of prematurity‑related IVH/PHVD and PHH
is still evolving and the treatment paradigms are constantly
changing from time to time since past few decades. Treatment
goals have now shifted from saving life to optimizing cognitive
function, neurodevelopment, and quality of life in premature
infants. The importance of early intervention with clearing the
blood and its breakdown products from the ventricles has been
realized by all and the newer techniques have been devised
or modified for a safe and effective treatment and improved
long‑term outcome. In this respect, the preliminary results of
newer techniques like VSGSs and NEL are promising. Based
on the recent literature, the contemporary management of
IVH/PHH recommends early diagnosis and intervention
using temporizing measure (VSGS, or NEL) and prevention of
future complications of PHH with a permanent CSF diversion
method such as ventricular shunting or ETV. Since the cognitive
outcomes are now considered more relevant, the future work
should be directed toward identifying earlier biomarkers of
cognitive neurodevelopmental outcome in order to define safe
and more effective treatment protocols.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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56. Mallucci CL, Jenkinson MD, Conroy EJ, Hartley JC, Brown M,
Dalton J, et al. Antibiotic or silver versus standard ventriculoperitoneal
shunts (BASICS): A multicentre, singleblinded, randomised trial and
economic evaluation. Lancet 2019;394:1530–9.
57. Gebert A‑F, Schulz M, Schwarz K, Thomale U‑W. Longterm survival
rates of gravity‑assisted, adjustable differential pressure valves in
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58. Warf BC, Campbell JW, Riddle E. Initial experience with combined
endoscopic third ventriculostomy and choroid plexus cauterization
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59. Chamiraju P, Bhatia S, Sandberg DI, Ragheb J. Endoscopic
third ventriculostomy and choroid plexus cauterization in
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60. Etus V, Ceylan S. Success of endoscopic third ventriculostomy in
children less than 2 years of age. Neurosurg Rev 2005;28:284–8.
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shunts: management of posthemorrhagic hydrocephalus in premature
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 Review Article

Access this article online

Quick Response Code:
Post‑Infective Hydrocephalus
Kanwaljeet Garg, Deepak Gupta

Abstract:
Background: Post‑infective hydrocephalus (PIH) arises as a complication of any CNS infection, and can be
Website: either communicating or noncommunicating.
www.neurologyindia.com
Objective: The aim of this article is to study the various causes of PIH and its pathophysiology and treatment.
DOI: Material and Methods: The literature was searched for articles describing the causes of PIH.
10.4103/0028-3886.332273 Results: Common causes of PIH are CNS tuberculosis (TB), neurocysticercosis, and perinatal or neonatal
infection. TBM is most likely to result in hydrocephalus out of all these manifestations of CNS TB, and
hydrocephalus is more likely to occur early in the course, typically 4–6 weeks after the onset of TBM, and is
more common among children as compared to adults. A trial of medical management (antitubercular therapy,
steroids, and decongestants) can be given to patients with communicating hydrocephalus. Ventriculoperitoneal
shunt is the most employed method of CSF diversion in these patients. Though traditionally considered
contraindicated, many recent studies have found ETV to be a reasonable option in patients with PIH. HCP in
patients with neurocysticercosis can be associated with intraventricular cysts and racemose cysts in the basal
subarachnoid cisterns. Surgical intervention is required either for cyst removal or CSF diversion. Endoscopic
approaches can be used to remove the intraventricular cysts, which takes care of the HCP. PIH in infants
can result either from antenatal infections (TORCH infections) or postnatal infections such as meningitis.
Conclusions: Management of PIH can be challenging. Management has to be individualized.
Key Words:
Endoscopic third ventriculostomy, hydrocephalous, neurocysticercosis, post‑infective, tubercular meningitis,
VP shunt

Key Message:
Post‑infective hydrocephalus (PIH) arises as a complication of any CNS infection and can be associated
with meningitis. Common causes of PIH are CNS tuberculosis, neurocysticercosis, and perinatal or neonatal
infection. Management options include medical management; CSF diversion procedures, including different
types of shunts; and endoscopic procedures, including septostomy and endoscopic third ventriculostomy.

H ydrocephalus is the most common

neurosurgical ailment. The prevalence
of HCP varies significantly depending on the
geographical location and income status of
the countries, with a higher prevalence being
reported from low‑ and middle‑income countries.
A recent meta‑analysis estimated the prevalence
of HCP to be 88/100,000 in the pediatric age
group, 11/100,000 in adults, and 175/100,000 in
the elderly.[1]
Department of
Neurosurgery, All India
It can arise de novo or it can be secondary to
Institute of Medical
other pathologies such as tumors, infection, or
Sciences, New Delhi,
subarachnoid hemorrhage. When HCP arises
India
because of any infective agent, it is termed as
Address for
post‑infective hydrocephalus (PIH). It is usually
correspondence: associated with meningitis, though not always.
Prof. Deepak Gupta, Out of all causes of HCP, PIH is one of the most
Department of difficult to manage.
Neurosurgery, Room
no 714, CNC, All India This is an open access journal, and articles are distributed under the terms
Institute of Medical of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0
Sciences, New Delhi, License, which allows others to remix, tweak, and build upon the work
India. non‑commercially, as long as appropriate credit is given and the new
creations are licensed under the identical terms.
E‑mail: drdeepakgupta@
gmail.com For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com
Li et al.[2] proposed the following criteria to
identify infants suffering from post‑infective
hydrocephalus in infants: (a) no history of
hydrocephalus at birth; (b) either a history
of seizure or febrile illness preceding the
development of hydrocephalus; and (c) imaging
findings suggestive of prior ventriculitis such
as scarring, loculations, or endoscopic findings
such as thickened ependyma or purulent
intraventricular debris. Chatterjee et al. [3]
proposed more objective criteria for the diagnosis
of PIH in children:
(a) Infants born with normal‑sized heads with
subsequent development of hydrocephalus
(b) History of febrile illness after birth
(c) CSF obtained from the ventricular tap
with any two of the following aspects: cell
count >100 cells/mm3, sugar level below
20 mg/dl, protein level >150 mg/dl, and
positive CSF culture.
How to cite this article: Garg K, Gupta D. Post-
Infective Hydrocephalus. Neurol India 2021;69:S320-9.
Submitted: 04‑Jul‑2021 Revised: 31-Aug-2021
Accepted: 20-Sep-2021 Published: 11-Dec-2021

S320 © 2021 Neurology India, Neurological Society of India | Published by Wolters Kluwer - Medknow
 Garg and Gupta: Post‑infective hydrocephalus
There are no specific criteria for diagnosing PIH in adults.
However, the history of any antecedent central nervous
system (CNS) infection (meningitis or ventriculitis) in adults
makes the diagnosis of PIH easier in this age group.
PIH can be either communicating or noncommunicating.
Communicating hydrocephalus results from impaired CSF
absorption because of the damage of the arachnoid villi and
subarachnoid spaces due to scarring.[4] Noncommunicating
hydrocephalus results from the obstruction of the normal CSF
circulation by space‑occupying lesions such as tuberculomas,
neurocysticercosis (NCC), or by formation of septa, etc.
Causes of PIH
Common causes of PIH include
1. CNS tuberculosis
2. Neurocysticercosis
3. PIH in infants
a. PIH due to perinatal infection
b. PIH due to neonatal infection.
Hydrocephalus associated with CNS tuberculosis
CNS tuberculosis accounts for 10% of all cases of tubercular
infection.[5] However, it is one of the most severe forms of
tuberculosis (TB) out of all the extrapulmonary forms of TB
as it is associated with high morbidity and mortality due to
its devastating complications. It is predominantly a disease
of populations living in overcrowded places in low‑ and
middle‑income countries.
There is hematogenous spread of tubercular bacilli when
there is an infection anywhere in the body. These bacilli
can settle in the CNS, and depending on many known and
unknown factors, such as host immunity, can lead to CNS
tuberculosis. The various forms of CNS tuberculosis include
TB meningitis (TBM), tuberculoma, tubercular abscess, and
tubercular vasculopathy.[6]
CNS tuberculosis can result in both communicating and
noncommunicating hydrocephalus. Basal meningitis is a
common feature of tubercular meningitis, which results in
communicating hydrocephalus. Some patients may develop
obstructive hydrocephalus due to obstruction of CSF pathways
by, for example, third tuberculomas.[7,8]
TBM is most likely to result in hydrocephalus out of all these
manifestations of CNS TB [Figure 1]. Hydrocephalus is more
likely to occur early in the course, typically 4–6 weeks after
the onset of TBM, and is more common among children as
compared to adults.[9,10] HCP is associated with poor prognosis
in patients with TBM.[11–13] High morbidity and mortality (up to
20%–50%) has been reported to be associated with TBM despite
the highly efficacious antitubercular treatment.[14]
In a recent study, 65% (52 out of 80) of the patients with TBM
had HCP at the time of presentation and another 10% developed
HCP during follow‑up.[12] The factors that predispose patients
with TBM to develop HCP include, but are not limited to,
advanced stage of the disease, severe disability, duration
of illness >2 months, diplopia, seizures, visual impairment,
papilledema, cranial nerve palsy, hemiparesis, CSF total cell
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S321
count >100/cu.mm, and CSF protein >2.5 g/l.[12] Presence of
basal exudates, infarcts, and tuberculomas are radiological
findings associated with the presence of HCP.
TBM is usually associated with communicating hydrocephalus
due to overproduction of CSF and decreased absorptive
capacity.[15] Noncommunicating HCP is less commonly seen to
be associated with TBM and occurs secondary to blockage of
fourth ventricular outlet by thick exudates or leptomeningeal
scarring.[12]
Several grading scores have been proposed for grading TBM
for disease severity and prognostication. The popularly used
grading systems are MRC grading, Vellore grading system,
and modified Vellore grading system [Table 1].[16,17]
Management of TBM with HCP
Medical management
A trial of medical management can be given to patients with
communicating hydrocephalus who are conscious and do
not have any deficit.[15] The rationale of a trial of medical
management is the hope that medical management will abate
the pathological processes, such as basal exudates, resulting
in hydrocephalus. Decongestants can be given for the initial
period to control the raised ICP while the antitubercular
therapy  (ATT) controls the inflammation and reverses the
pathophysiological changes behind the communicating
hydrocephalus.
Medical management includes ATT, steroids, decongestants,
and antiepileptics. The regimen of ATT and the total duration
of therapy have been a matter of debate.[18] Four drug regimen
is the most followed drug regimen and includes the concurrent
administration of isoniazid 5 mg (4–6 mg/kg), rifampicin
10 mg (8–12 mg/kg), pyrazinamide 25 mg (20–30 mg/kg), and
ethambutol 15 mg (15–20 mg/kg).[19,20] It has been suggested to
Table 1: Grading of tubercular meningitis with
hydrocephalous
Vellore grade
Grade
I Headache, vomiting, fever±neck stiffness
No neurological deficit
Normal sensorium
II Normal sensorium
Neurological deficit present
III Altered sensorium but easily arousable
Dense neurological deficit may or may not be present
IV Deeply comatose
Decerebrate or decorticate posturing
Modified Vellore grade
I GCS 15
Normal sensorium and no neurological deficit
Headache, vomiting, fever±neck stiffness
II GCS 15
Normal sensorium with neurological deficit
III GCS 9‑14
Neurological deficit may or may not be present
IV GCS 3‑8
Deeply comatose with or without decerebrate/decorticate
posturing
 Garg and Gupta: Post‑infective hydrocephalus

a b

c d
Figure 1: MRI of a patient with TBM associated with hydrocephalus showing hydrocephalus (a and b) and basal meningitis (c). Artifact of the shunt can be noted in the left
occipital area (c). Noncontrast CT done a few weeks later showing decompression of the ventricular system (d)

replace ethambutol with streptomycin 15 mg (12–18 mg/kg)
and to prolong the duration of ATT to 9–12 months in case of
TBM with HCP.[10,18,21] ATT, besides being antibacterial, has
anti‑inflammatory action.
Steroids have been shown to have a positive impact on
mortality.[22] This effect was found to be more profound in
patients who were drowsy or those who received steroids
for at least 10 days.[22] A randomized controlled trial studying
the impact of steroids on patients with TBM concluded that
adjunctive steroids improve survival without any impact
on the functional outcome of patients more than 14 years of
age.[19] However, this study did not comment on the role of
steroids on HCP present along with TBM.[19] Commonly used
dose of parenteral dexamethasone in sick patients with TBM
is 0.2 mg/kg/day in divided doses.[10]
Commonly used decongestants include diuretics such as
furosemide or agents such as mannitol. Acetazolamide can
be helpful in decreasing ICP by reducing CSF production.
Decongestants can decrease ICP and improve cerebral
perfusion pressure. This also results in better delivery of ATT
in the CNS.
Two series have shown medical management to be effective
in 15.1% and 22% of patients with communicating HCP
secondary to TBM.[23,24] Rajshekhar et al.[15] recommended a
trial of medical management in patients with communicating
HCP who are better grade (Vellore grade II). However, these
patients with communicating hydrocephalus need to be under
close neurological monitoring.
Surgical management
Surgical treatment of hydrocephalus secondary to TBM has
been described in the literature for more than seven decades.
Cairns described making frontal burr holes and drainage of
CSF in patients with raised ICP secondary to TBM.[25] He also
described his experience of intraventricular instillation of
streptomycin. Bhagwati described his experience of inserting
ventriculoatrial shunt in seven patients with TBM with HCP.[26]
He reported improvement in the clinical state of the patients,
including improved vision in children who were blind for
4–6 weeks. He suggested that a CSF diversion procedure
should be done early in the course without fearing systemic
dissemination of the bacilli. Many other authors have shown
the efficacy of CSF diversion procedures in these patients.[15,27]
Indications and timing of CSF diversion
All patients with obstructive hydrocephalus should undergo
CSF diversion if indicated clinically. The indications and
timing of CSF diversion in patients with communicating
hydrocephalus secondary to TBM have been debated in
different studies. Some recommend early shunt in patients
with Grade 1 and 2 disease as it has been shown that the
outcomes are better if CSF diversion is done early.[15] However,
there are others who recommend medical management first in
these patients as permanent shunt insertion can be avoided in
a significant number of patients.[23] We go for CSF diversion
procedures depending on the clinical condition of the patient.
We recommend urgent CSF diversion even in a conscious
patient if he/she has raised ICP signs and symptoms along
with papilledema on fundus examination and hydrocephalus
on CT without delay. Similar strategy has been supported by
the literature.[28]
Types of CSF Diversion
1. External ventricular drain (EVD) ‑ The indications of
inserting an external ventricular drain are clearly defined.
It is recommended in patients with HCP who present in an
unconscious state as a temporary measure before the patient
undergoes permanent CSF diversion procedure. Moreover, it
has been recommended that patients with the higher‑grade
disease (Grade IV) should undergo an EVD first to ascertain
that the HCP is the cause of neurological deterioration.[16,17]

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 Garg and Gupta: Post‑infective hydrocephalus

2. Ventricular shunts ‑ Ventriculoatrial shunts (VA shunt)
have been used for a long time in patients with TBM and
HCP, much before ventriculoperitoneal shunts (VP shunts).
Many studies from India have shown successful use of VA
shunt in these patients[26,29] and contradicted the theoretical
risks of dissemination of the tubercular bacilli.
VP shunt became the procedure of choice for these patients
in the 1980s as the surgical procedure is less challenging
as compared to VA shunt [Figure 1]. However, it might be
tricky to insert the distal end in the presence of peritoneal
adhesions in patients with concomitant tubercular
peritonitis. Another option in patients with peritoneal
adhesions is ventriculopleural shunt, which can be done
in children of age 8 years or more. Ventriculocholecystic
shunt (VC shunt) with the distal end placed in the
gallbladder can serve as an option where all other options
have been exhausted.[30,31] Venticulogastric shunt has
also been tried in patients who have undergone multiple
revisions of ventriculoperitoneal shunt [Figure 2].
A recent meta‑analysis reported the pooled complication
rate following VP shunt to be 22%, and the commonest
complications included shunt block, shunt infection, and
intraventricular hemorrhage.[32]
Different types of shunt systems are available, such
as programmable shunts, fixed pressure shunts, and
antibiotic‑impregnated shunts. However, the currently
available literature has not shown the superiority of any
one type of shunt system over the other.[33–35] This in itself
is a matter of debate and an extensive topic that is beyond
the scope of this article.
3. Endoscopic procedures – Traditionally, PIH has been
considered to be a contraindication for endoscopic
third ventriculostomy (ETV) as the CSF absorption is
compromised due to the presence of scarring of arachnoid
villi and subarachnoid spaces. However, many recent
studies have found ETV to be a reasonable option in
patients with PIH, with success rates varying from 41% to
81%.[4,36–40] It is definitely useful in patients with obstructive
hydrocephalus but can also be tried in patients with
communicating hydrocephalus.
It has been seen that patients who have received ATT
for a longer time and have longer‑duration disease did
better with ETV. In contrast, patients with a higher grade
of illness, cisternal exudates, distorted third ventricular
floor anatomy, and dense adhesions in prepontine cisterns
have been found to have a poor prognosis. A randomized
controlled study comparing ETV and VP shunt for
hydrocephalus in TBM observed that the relative risk of
ETV failure is higher than that for VP shunt.[38] However,
the risk of failure was found to decrease over time.
ETV in these patients is technically challenging as the
third ventricular floor is thick and opaque in the acute
phase of the disease.[41,42] The water jet dissection technique
can be used to create stoma in patients with opaque
third ventricular floor.[41,42] A recent study suggested that
ETV should be attempted in patients with obstructive
hydrocephalus due to TBM only in the chronic stage.[43]
4. Lumboperitoneal shunts ‑ Lumboperitoenal shunt is always
an option in patients with communicating hydrocephalus.
There are studies that have found lumboperitoneal
shunt to be a safe and effective strategy in patients with
communicating HCP secondary to TBM.[44,45] However, it
is not the first‑choice procedure in these patients as it has
a high chance of blockage and CSF flow is unregulated as
it is valveless.
Outcomes following VP shunt in TBM with HCP
The outcome following CSF diversion procedures in patients
with TBM with hydrocephalus is not uniform and besides
other factors, depends on the grade of TBM. The cause of poor
outcomes despite CSF diversion can be encephalitis or infarcts
secondary to tubercular arteritis.[15] A recent meta‑analysis
reported an overall good outcome (Glasgow Outcome Scale)
in 58.26% of patients following VP shunt.[32] The rate of good

a b

c d e
Figure 2: Two‑year‑old boy, born by full‑term normal vaginal delivery. He developed necrotizing enterocolitis in the postnatal period and underwent colostomy for the same in
September 2018. He was diagnosed with post‑meningitic hydrocephalus for which ventriculo‑subgaleal shunt (VSG) was done in January 2019. VSG shunt was converted to
a left‑sided VP shunt in September 2019. He underwent multiple shunt revisions for shunt blockage. He underwent ETV, right frontal shunt removal, and right frontal Ommaya
placement on November 26, 2020 (a and b). He underwent revision of right occipital shunt and removal of right frontal Ommaya (c and d). However, her occipital shunt got
blocked in 2 months (e) and she underwent ventriculogastric shunt

Neurology India | Volume 69 | Supplement 2 | November-December 2021 S323

 Garg and Gupta: Post‑infective hydrocephalus
outcomes in patients with grade I, II, III, and IV TBM was
78.57%, 65.35%, 67.97%, and 31.51%, respectively, in this
study. These findings suggest that VP shunt should be done
at the earliest available opportunity in patients with TBM
and HCP as the outcomes worsen with worsening grades of
TBM and HCP. It has been suggested by some to go for VP
shunt in patients with grade IV TBM only when there is an
improvement following EVD insertion, considering the poor
outcomes. However, this has been challenged by a study
that demonstrated good outcomes in 18% of patients with
grade IV disease who showed no improvement following EVD
insertion.[46] The outcome also depends on the type of HCP with
obstructive HCP being reported to be associated with better
outcomes than communicating HCP.[23,47]
It must be mentioned that VP shunt does not prevent death in
all patients with TBM and HCP. The mortality rate following
VP shunt in these patients was reported to be 18.03% in a
meta‑analysis involving 743 patients.[32] It has been suggested
that the inherent immune responses of an individual patient
may have some role to play in the final outcome. This is further
strengthened by the fact that the mortality in patients with TBM
who have HIV following VP shunt is 66.67%.[32,47]
Other causes of HCP in CNS tuberculosis
Lesions such as tuberculoma can also lead to hydrocephalus.[7,48]
This can be treated by a VP shunt. Sometimes, a biopsy of the
lesion is required to confirm the diagnosis, which can be done
using endoscopic techniques.[48]
Hydrocephalus due to neurocysticercosis
Neurocysticercosis results from CNS infestation by the
larval stage of the pork tapeworm, Taenia solium, and is
the most common helminthic infection in humans. Though
it is limited to developing countries due to poor sanitation
conditions, it accounts for nearly 50,000 deaths per year.[49]
Hydrocephalus is a less common manifestation in patients
suffering from NCC, with seizures and raised ICP (secondary
to cerebral edema, encephalitis, or hydrocephalus) being
the most common manifestations. Nevertheless, HCP can
be the cause of clinical presentation in up to 15%–30% of
patients with NCC. It is important to differentiate between
the parenchymal and extraparenchymal forms of NCC as the
clinical presentation and age groups are different in these two.
The parenchymal form occurs more commonly in children and
presents with seizures, whereas the extraparenchymal form is
likely to present with raised ICP and is associated with higher
mortality due to raised ICP. Genetic predisposition to NCC
and the type of NCC based on the metalloproteinase‑9 gene
polymorphism and Toll‑like receptor‑4 gene polymorphism
has been proposed.[50–54]
Pathogenesis of HCP in NCC
HCP in patients with NCC can be associated with
intraventricular cysts and racemose cysts in the basal
subarachnoid cisterns [Figure 2]. Basal meningitis can also block
the fourth ventricular outlet, leading to obstructive HCP.[55]
Occasionally, HCP can result from cysticercoticarachnoiditis
and granular ependymitis.[49]
The intraventricular NCC tends to settle in the subarachnoid
spaces in the brain and spine, including the basal cisterns,
S324 Neurology India | Volume 69 | Supplement 2 | November-December 2021
and can enter the ventricular system.[50] Blockage of the CSF
pathway at any point can result in obstructive HCP, which is
by far the most common type in patients with NCC. The fourth
ventricle is the most common location of intraventricular NCC,
perhaps due to the effect of gravity and direction of normal
CSF flow.
Diagnosis
It is important to differentiate between obstructive
hydrocephalus and communicating HCP due to NCC as
obstructive hydrocephalus can be managed using endoscopic
techniques and can be curative in many situations whereas VP
shunt is a lifelong liability as it can get blocked anytime. One
needs to have a high index of suspicion to consider NCC as a
differential in a patient presenting with HCP to the emergency
department. Neurocysticercosis is difficult to be picked up on
CT as the cysticercus cyst is isodense to CSF. MRI, especially
sequences such as 3D constructive interference in steady
state (CISS), is the best tool to identify the NCC blocking the
CSF pathway resulting in HCP.
Eosinophilia on peripheral smear can be a soft indicator of
the presence of a helminthic infestation. CSF immunoglobulin
levels and enzyme‑linked immunoelectrotransfer blot (EITB)
can also help in making the diagnosis, with the latter having
very high sensitivity (~98%) in patients with two or more
viable cysts. However, ETIB has low specificity for NCC;
enzyme‑linked immunosorbent assay (ELISA) can be used
instead and has high sensitivity and specificity (89% and 93%,
respectively) in patients with viable neurocysticercosis.[56]
Surgical management of HCP
Surgical intervention is required either for cyst removal or
CSF diversion [Figure 3]. Endoscopic approaches can be used
to remove intraventricular cysts, which take care of the HCP.
These cysts can shift position frequently from one region to
another, making endoscopic removal challenging. Thus, an
imaging study should be done just before shifting the patient
to the operating room to avoid intraoperative surprises.
One needs to be aware of different techniques that can be
used to remove cysts from the fourth ventricle as it is the
most common location of cysts causing HCP. An endoscopic
“scope in scope” approach has been proposed for the fourth
ventricular cysts, where a flexible endoscope is passed through
a rigid endoscope.[57] Sharma et al.[58] described the use of an
infant feeding tube through the endoscope channel to remove
the NCC in the lateral third or fourth ventricle. The tip of the
infant feeding tube is cut smooth proximal to the openings.
This tip is kept on the cyst wall and gentle suction is applied
using a 20‑cc syringe and the intact cyst is removed along with
the endoscope. They recommended performing ETV after
removal of the cyst in presence of pericystic inflammation
and/or ependymal reaction (enhancement on contrast); ETV
is recommended.
Cyst excision alone may suffice in patients with a single
cyst. However, patients who have some residual cysts left
in the ventricular system need antihelminthic drugs such as
albendazole (15 mg/kg/day) for 2 weeks.[59]
CSF diversion in the form of a VP shunt may be required
in patients with other types of HCP secondary to NCC.
 Garg and Gupta: Post‑infective hydrocephalus
a b c
Figure 3: Noncontrast CT (a) and MRI (b) of a patient (a known case of
neurocysticercosis) showing ventriculomegaly with periventricular ooze.
A zoomed‑in image (c) of the fourth ventricle of the same patient showing
neurocysticeri cysts in the fourth ventricle
There is a risk of shunt blockage due to the high protein
content of CSF or obstruction of the shunt by intraventricular
cysticerci or inflammatory exudates. These patients may
need shunt revision frequently like in other causes of PIH.[50]
Patients with communicating HCP can develop obstructive
HCP over the course of time if the primary disease is not
controlled.[50] Another complication of a VP shunt in patients
with intraventricular NCC is the migration of cysticerci from
the fourth ventricle proximally to the lateral or third ventricle
due to the “siphon effect.”[60] The fourth ventricle may get
trapped mandating suboccipital craniotomy and removal of
the cysticerci.[50] The outcome of these patients following VP
shunt or neuroendoscopic interventions varies significantly
and depends on the course of the underlying disease.[50,60]
Some patients get cured whereas in others the disease follows
a relentless course resulting in significant morbidity.[50,58]
PIH in infants
PIH in infants can result either from antenatal infections or
postnatal infections.
PIH due to perinatal infections
PIH can be one of the manifestations of antenatal infections,
notably TORCH infections. The variation of fetal affliction
following antenatal infection varies from asymptomatic
infection to fetal malformations incompatible with life.
Pathogenesis of PIH is very well described in pediatric
patients and depends on the infectious agent and the age of
the patient at the time of infection.[4,61] Prenatal toxoplasmosis
results in hydrocephalus due to leptomeningeal inflammation
and ependymal erosive necrosis.[4,62–64] Inflammatory debris
resulting from infection can also block the aqueduct.
Encepahlomalacia leading to volume loss is the most
common cause of hydrocephalus following infection by
cytomegalovirus (CMV), though its incidence is quite low.[4,64]
PIH due to neonatal infections
Neonatal infections, such as sepsis and meningitis, can lead
to communicating hydrocephalus early in the course of the
disease. These infections are most commonly caused by
coagulase‑negative staphylococci followed by other gram‑positive
and gram‑negative organisms.[64,65]
Infections by gram‑negative bacteria, on the contrary, are
more likely to result in multiloculated hydrocephalus as they
result in ventriculitis. Haemophilus influenzae  (H. Inf) is a
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S325
a b c
Figure 4: CT scans of a 5‑year‑old child, previously operated case of brainstem
glioma. He had a right occipital VP shunt in situ and developed shunt infection.
NCCT (a and b) shows the ventricular dilation of all the ventricles with a right
occipital ventricular catheter in situ and third ventricular diverticulum. His VP shunt
was removed and a long‑tunnel EVD was inserted. He also underwent endoscopic
ventricular lavage. He developed intraventricular adhesions
common cause of meningitis in slightly older infants. However,
hydrocephalus is a relatively uncommon complication of H. inf
infection as choroid plexitis results in less CSF production and
basal meningitis is also less common.[64]
Management of PIH in neonates/infants
Management of PIH in neonates and infants is very challenging.
There are some unique problems with this age group.
An EVD can be inserted when the CSF is meningitic or when
the patient presents with acute hydrocephalus. However,
there are many disadvantages of EVD in this age group; for
instance, it is difficult to control the rate of CSF drainage in
these patients due to the smaller volume of CSF and there is a
risk of overdrainage. Moreover, EVDs are difficult to manage
in infants and there is a risk of spread of infection from outside
atmosphere to inside the ventricular cavity.
VP shunt is another option. First, VP shunts are not well
tolerated by infants who weigh less than 2 kg. Moreover, many
of these neonates are immature, with immature peritoneum
with limited absorptive capability. Many of these patients
have associated abdominal pathologies such as necrotizing
enterocolitis, ruling out a successful abdominal surgery. The
chances of shunt blockage are also high given high levels
of protein in the CSF can be inserted only when the CSF is
nonmeningitic.
ETV is not recommended in neonates given the technical
difficulties and poor outcomes due to poor absorptive capacity.
Ventricular access devices are another option, such as the
Ommaya reservoir, which is relatively commonly used.
However, one must keep in mind that these reservoirs need
to be tapped frequently to drain CSF and relieve raised ICP.
It is very cumbersome to tap these devices apart from the risk
of increased infection every time it is tapped. There is a risk
of CSF leakage through the skin after repeated tapping as the
skin of neonates is thin. Thus, it is not a permanent solution
rather a temporary measure.
Ventriculo‑subgaeal shunt is another option, which involves
connecting the ventricular cavity with a subcutaneous pouch
through a valve‑less catheter.[66,67] It is commonly used for
posthemorrhagic hydrocephalus in premature children but
can also be used in cases of PIH. It overcomes many of the
shortcomings of the procedures described above and can
 Garg and Gupta: Post‑infective hydrocephalus
be used as a temporary measure till the child can tolerate a
permanent procedure such as VP shunt.
Multiloculated HCP or Complex HCP
Multiloculated hydrocephalus (MLH) is an entity where
the ventricular system is divided into independent multiple
compartments by the formation of impermeable septa.[68,69]
These compartments tend to enlarge despite a functioning
shunt.[70] Intraventricular infection or ventriculitis is a common
cause of MLH [Figure 4].
Ventriculitis, due to any cause, can lead to MLH. Ventriculitis
damages the ependymal lining, exposing the underlying glial
cells to CSF. Glial cells can act as a nidus upon which fibro‑glial
septations can develop, leading to isolated compartments of
CSF.[4,71] The septations thus formed may progress and become
impermeable to CSF if the infection is not treated.[70] Multiple
septations formed may divide a single ventricular cavity into
multiple small compartments, some of which may get isolated
later on, further complicating the management.
More importantly, an endoscope can be used for “simplification”
of MLH or complex hydrocephalus.[72] It pertains to septostomy,
foraminoplasty, etc., which convert multiple independent
ventricular cavities into one or two cavities, thus limiting
the number of CSF diversion catheters. Staged endoscopic
procedures to adequately communicate multicompartmental
hydrocephalus should be considered before the placement of
a second shunt.[72] Many recent studies have highlighted the
role of CT ventriculography to identify the blockage to the
physiological flow of CSF.[68,73]
External ventricular drain
External ventricular drains (EVD) are commonly used
as a temporary measure to decompress the ventricular
system when there is hydrocephalus and CSF is meningitic
before a permanent CSF diversion procedure can be done.
Usually, an EVD is kept for 5–7 days before it needs to be
replaced. However, the distal end of an EVD can be taken
out more distally (long‑tunnel EVD) than the routine 5‑cm
tunnel (standard EVD) to decrease the risk of infection, which
increases if it is kept for a prolonged period.[74,75]
Soleman et al.[76] investigated if the conversion of an EVD to a VP
shunt without replacing the ventricular catheter increases the
risks of shunt infection or shunt malfunction. They concluded
that it is safe to do so without any increased risk of infection.
Zhang et al.[77] assessed the therapeutic efficacy of EVD in
patients with PIH and studied the need and predictors of the
need for a permanent CSF diversion procedure in infants with
post‑infective hydrocephalus (PIHC). They observed that 64.5%
of patients needed a permanent CSF diversion after PIH. The
patients who needed permanent CSF diversion needed EVD
for a longer period and had a higher frontal and occipital
horn ratio.
Other endoscopic procedures in PIH
Asymmetric hydrocephalus can be treated by septum
pellucidotomy or opening of the blocked foramen of Monro.
Isolated frontal horn can be treated by communicating with
the rest of the ventricle or fenestration of septum pellucidum.
S326 Neurology India | Volume 69 | Supplement 2 | November-December 2021
Isolated fourth ventricles can be treated with aqueductoplasty
and aqueductal stenting. Aqueductoplasty establishes
communication between the isolated ventricular compartments,
and the stent is mandatory to keep the communication open
and avoid reclosure. Moreover, ventricular lavage can also be
helpful in clearing the debris inside the ventricular system,
resulting in early clearance of infection in patients with
ventriculitis and hydrocephalus.[78]
Retrieval of a ventricular catheter stuck to the choroid plexus
carries a high risk of intraventricular hemorrhage. The
nonfunctioning catheters should be taken out as they can act
as a nidus for infection. Retrieval of the migrated ventricular
end is done under vision with endoscopy. After coagulation
and division of adhesions, the catheter is held in forceps passed
through the endoscopic channel and removed with the whole
assembly.
Ventriculitis associated with shunt infection
There are high chances of shunt infection, and rates as high
as 10%–22% per patient and around 6.0% per procedure have
been reported in the literature.[79] Most of the shunt (nearly 90%)
infections occur within 30 days of surgery.[79] Many strategies
to decrease shunt infection rates have been tried, but there is
no definite way to prevent shunt infection.[33,80–85] There are
high chances of the development of ventriculitis following
bacterial shunt infection. Bacterial ventriculitis can lead to
purulent brain abscess and remains an important cause of
mortality and morbidity in patients with hydrocephalus. Pus
and debris should be drained on an emergent basis as it reduces
inflammation, thus preventing the formation of intraventricular
septae and isolated ventricles.[86]
These patients may require prolonged EVD insertion while
waiting for CSF infection to clear when a permanent CSF
diversion procedure can be implanted along with prolonged
intravenous or intrathecal antibiotics. [83,87] Endoscopic
procedures, as described above, can be used to deal with
multiple complications that can arise as a result of ventriculitis.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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Neurology India | Volume 69 | Supplement 2 | November-December 2021 S329

 Review Article

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Quick Response Code:
Hydrocephalus in Tuberculous
Meningitis ‑ Pearls and Nuances
Vimal K Paliwal, Ravindra K Garg1

Website: Abstract:
www.neurologyindia.com
Tuberculous meningitis (TBM) is associated with high mortality. A large proportion of patients with TBM, who
DOI: survive, live with disabling neurological sequelae. Hydrocephalus is one of the common complications of TBM,
10.4103/0028-3886.332275 seen in up to 80% of patients. Hydrocephalus may be a presenting feature or may develop paradoxically after
the commencement of antituberculosis treatment. The Hallmark pathological feature of TBM is a thick gelatinous
exudate, dominantly present at basal parts of the brain. Exudate encases and strangulates cranial nerve trunks
like optic nerve, optic chiasma, and vessels of the circle of Willis. Basal exudate also blocks the cerebrospinal
fluid  (CSF) flow in the brain, resulting in ventriculomegaly. It is often difficult to differentiate between two
common types (communicating and obstructive) of hydrocephalus on basis of routine neuroimaging.
Progressive hydrocephalus, clinically manifests with a potentially life‑threatening high intracranial pressure.
Patients with deteriorating vision loss and deteriorating consciousness, often need a surgical CSF diversion
procedure (ventriculoperitoneal shunt or endoscopic third ventriculostomy) to be performed. CSF diversion
may be life‑saving. However, the long‑term benefits of CSF diversion are largely unknown.
Key Words:
Endoscopic third ventriculostomy, Hydrocephalus: Ventriculo-peritoneal shunt,Tuberculous meningitis

Key Message:
Hydrocephalus is a common complication of TBM. When and how to treat hydrocephalus is not known with
certainty. Many patients require CSF diversion surgery, like ventriculoperitoneal shunt, endoscopic third
ventriculostomy. Unfortunately, the overall prognosis, even after shunt surgery remains unaffected.

T uberculous meningitis (TBM) is a devastating

infective disorder of the central nervous
system. Approximately, one‑third of patients
patients, it requires surgical intervention.
Ventriculoperitoneal shunt, endoscopic third
ventriculostomy, and external ventricular
with TBM die despite treatment. [1,2] TBM in drainage are neurosurgical procedures, that are
HIV‑infected persons is associated with an even used to treat TBM. Hydrocephalus is generally
poorer prognosis. [2,3] Altered consciousness, a poor prognostic marker. This review will
diabetes mellitus, immunosuppression, focus on the types of hydrocephalus in TBM, its
neurological deficit, hydrocephalus, and pathogenesis, its predictors, and the outcome of
vasculitis predict poor outcome. [4] TBM is available surgical options.
associated with a variety of complications
Department of
like hydrocephalus, periventricular infarcts, Incidence
Neurology, Sanjay
optochiasmatic and spinal arachnoiditis, and
Gandhi Postgraduate
tuberculous mass lesions in the brain.[5] All these Hydrocephalus is seen in up to 80% of children
Institute of Medical
complications adversely affect the outcome of with tuberculous meningitis.[5‑7] In a small study
Sciences, Lucknow,
TBM. In children, up to 80% of survivors may comprising of only 38 children, a cranial CT
Uttar Pradesh,
suffer a life‑long disability.[5] showed hydrocephalus in 31 (94%) patients.[8]
1
Department of
Neurology, King In adults as well, hydrocephalus is a frequent
Hydrocephalus is easily diagnosed by both CT complication of TBM.[9‑11] In a study, Raut et al.,
George Medical
and MRI scans. However, MRI scan is considered included 80 patients with TBM, hydrocephalus
University, Lucknow,
superior to diagnose hydrocephalus and to was recorded in 65% (52/80) patients.
Uttar Pradesh, India
identify associated tuberculomas, basal exudates, Thirty‑two (61.5%) patients had moderate to
Address for and infarcts. Hydrocephalus is mostly managed severe hydrocephalus.[11] Ozates et al. reviewed
correspondence: with medical management. In a minority of
Prof. Ravindra K Garg,
Department of Neurology, This is an open access journal, and articles are distributed under the terms How to cite this article: Paliwal VK, Garg RK.
King George Medical of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 Hydrocephalus in Tuberculous Meningitis - Pearls and
University, Lucknow, License, which allows others to remix, tweak, and build upon the work Nuances. Neurol India 2021;69:S330-5.
Uttar Pradesh, India. non‑commercially, as long as appropriate credit is given and the new
creations are licensed under the identical terms. Submitted: 07‑Jul‑2021 Revised: 16‑Aug‑2021
E‑mail: garg50@yahoo. Accepted: 13‑Sep‑2021 Published: 11-Dec-2021
com For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com

S330 © 2021 Neurology India, Neurological Society of India | Published by Wolters Kluwer - Medknow
 Paliwal and Garg: Hydrocephalus in Tuberculous Meningitis ‑ Pearls and Nuances

CT of the brain in 289 patients (214 children, 75 adults) with

TBM, hydrocephalus was diagnosed in 204 patients.[10] In a
smaller study with 29 patients, hydrocephalus was seen in
six patients.[12] Tandon et al. noted that hydrocephalus was
present in all patients having a disease duration of four to
six weeks.[13]

Hydrocephalus is classified as communicating hydrocephalus

and non‑communicating or obstructive hydrocephalus.
In communicating type, obstruction to the flow of CSF
is either at the level of basal cisterns or there is impaired
absorption of CSF at the level of arachnoid granulations. In
the non‑communicating type, there is an obstruction to the
flow of CSF either at the level of the cerebral aqueduct or
at the outflow tract of the fourth ventricle. Communicating
hydrocephalus is commoner variety and it is seen in up to 80%
Figure 1: Contrast‑enhanced magnetic resonance imaging of brain shows thick
of patients.[14‑17] The site of obstruction can more precisely be basal exudates in optochiasmatic and periventricular area along with hydrocephalus
assessed by air‑encephalography or contrast ventriculography,
however, these imaging procedures are rarely performed. MRI
is a superior technique for identification of TBM associated
complications, Pienaar and colleagues observed that cranial
CT is equally efficient in diagnosing hydrocephalus in TBM
patients.[18] Singh and colleagues, in series of 35 TBM patients,
who were subjected to endoscopic third ventriculostomy,
54% of patients had obstructive hydrocephalus and rest 46%
communicating hydrocephalus.[19]

Pathogenesis

The current understanding of the pathogenesis of TBM is

largely based on post‑mortem studies, that were done in the
pre‑chemotherapy era. Mycobacterium tuberculosis, first infects
the lung via airborne transmission. Later, Mycobacterium
tuberculosis via hematogenous route spread to meninges
and subpial region of the brain, forming small tuberculous
granuloma, called “Rich’s focus”.[20] TBM develops when these Figure 2: Contrast‑enhanced magnetic resonance imaging of brain shows thick
“Rich’s focus” ruptures releasing Mycobacterium tuberculosis into exudates in right Sylvian fissure
the subarachnoid space and/or the ventricles. Subsequently,
there is an intense inflammatory reaction in the meninges and
adjacent brain parenchyma.[21] Alternatively, Mycobacterium
tuberculosis can reach directly to the brain and other body
parts in patients with miliary tuberculosis.[22] Pathological
hallmark of TBM is the formation of gelatinous exudates with
the propensity to affect the basal parts of the brain. Basal
exudates encase and strangulate optic chiasma and optic
nerves, major blood vessels, cranial nerves, and also obstruct
the CSF pathways. The obstruction to CSF pathways results
in ventriculomegaly. In communicating type of hydrocephalus
there is a mismatch between production and absorption of CSF.
When CSF flow is hindered thick exudates beyond foramen
of Luschka and Magendie in basal cisterns (particularly in
the inter‑peduncular cistern or the cisterna ambiens), there is
impaired absorption of CSF at arachnoid granulations.[23] The
obstruction of the cerebral aqueduct and the fourth ventricular
outflow by exudates produce non‑communicating or
obstructive hydrocephalus.[24] Frequently, the size of ventricles Figure 3: Computed tomography of brain shows marked ventriculomegaly with
may keep enlarging paradoxically, even after initiation of periventricular ooze
antituberculosis treatment.[25] Rarely, hydrocephalus can be
asymmetrical. Ependymitis and thick exudates in the ventricles Predictors of Hydrocephalus in TBM
can cause sequestration of the occipital or temporal horn of the
lateral ventricle or fourth ventricle resulting in asymmetrical Chen and colleagues, in a prospective, follow‑up study of 31
ventriculomegaly [Figures 1‑4].[26] TBM patients, noted incidence and associated clinical features
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S331
 Paliwal and Garg: Hydrocephalus in Tuberculous Meningitis ‑ Pearls and Nuances
Figure 4: Magnetic resonance imaging (FLAIR images) of brain shows left‑sided
periventricular infarct
of hydrocephalus and assessed the impact of hydrocephalus
on the outcome. The follow‑up period was up to 57 months.
Initial evaluation revealed hydrocephalus in 9 patients, while
22 developed hydrocephalus paradoxically after initiation of
anti‑tuberculosis drugs. A long duration of illness, advanced
stage of TBM, focal neurological deficit, and infarcts predicted
hydrocephalus. Hydrocephalus was associated with poorer
outcomes.[25] Raut and colleagues, in a large (80 patients)
prospective study, noted that vision impairment, cranial
nerve palsies, and basal meningeal enhancement significantly
predicted the development of hydrocephalus, during 6 months
of follow up period. The presence of hydrocephalus, at
inclusion, was associated with death or severe disability.[11]
Clinical Manifestations
Headache, vomiting, fever, altered consciousness, vision loss,
signs of meningeal irritation, cranial nerve palsies, focal deficits,
and seizures are characteristic clinical features of TBM. Duration of
illness, classically, exceeds 5 days. CSF examination characteristically
shows lymphocytic‑predominant pleocytosis, increased proteins,
and low glucose levels. Mycobacterium tuberculosis in CSF is
conventionally demonstrated either by smear examination for
acid‑fast bacilli or by culture. Genotypic nucleic acid amplification
tests, like Gene‑Xpert, a CBNAAT (cartridge‑based nucleic acid
amplification test), are readily available and results are available
in 4 hours. Raut and colleagues noted that in patients with TBM
with hydrocephalus, seizures, diplopia, cranial nerve involvement,
vision loss, papilledema, and optic atrophy were more frequent
as compared to those patients without hydrocephalus.[11] Patients
with deteriorating consciousness, vision loss, asymmetric pupils,
papilledema, ophthalmoplegia, and extensor plantar responses,
a possibility of evolving hydrocephalus should be kept and
neuroimaging should urgently be performed. Patients of TBM
with sequestered and asymmetrical ventricles often present with
raised intracranial pressure and need an emergency surgical
intervention.[26]
Neuroimaging
CT alone is a satisfactory neuroimaging option to identify
hydrocephalus in patients with TBM. [Figure 3] Objectively,
S332 Neurology India | Volume 69 | Supplement 2 | November-December 2021
hydrocephalus is recognized with the help of Evan’s ratio.
Evan’s ratio is a ratio of the maximum width of frontal horns
to the maximum width of the inner skull. Evan’s angle was
originally calculated, in sagittal sections, on encephalograms.[27]
Normal Evan’s angle is less than 0.30. Evan’s angles of <0.34,
0.34 to 0.4, and >0.4 classify hydrocephalus as mild, moderate,
and severe hydrocephalus respectively. [28] In children,
frontal/temporal horn ratio and frontal/occipital horn ratio
may be calculated in the coronal plane, by ultrasound, to
assess the ventricular enlargement.[29] Objective criteria are
generally used for research purposes only. Dilated ventricles,
periventricular ooze, or trans‑ependymal egress of CSF
into the brain parenchyma, and effacement of overlying
sulci are usually sufficient to diagnose hydrocephalus
clinically.[18] Differentiation between communicating and
non‑communicating hydrocephalus is difficult by CT alone.
The presence of dilated fourth ventricle is usually seen
in communicating hydrocephalus whereas normal‑sized
fourth ventricle favors non‑communicating hydrocephalus.
MRI is more efficient in delineating the outline of the fourth
ventricle.[24]
Ventriculitis and sequestered ventricles are more clearly
visible on MRI. Gadolinium enhancement of ependymal
lining of ventricles, diffusion restriction of ependymal lining,
hyperintensity of ependyma on magnetization transfer images,
presence of ventricular sludge, and ventricular septations
suggest ventriculitis or ependymitis. Ventricular sludge is
visible on diffusion‑weighted as the area of restricted diffusion,
present on the dependent parts of lateral ventricles. The
trapped ventricle appears like an asymmetrical cystic mass
with profound periventricular ooze, mass effect, and midline
shift.[26]
Grading of Patients with TBM and Hydrocephalus
The most common grading system used to grade patients with
TBM is the Medical Research Council (MRC) grade that divides
patients into three grades based on the presence of neurological
deficit and severity of altered consciousness. Vellore grading
system was first introduced in 1991 and later modified in 1998
to classify patients with TBM and hydrocephalus. Vellore
grading system classifies TBM patients into four grades.
Grade IV patients are deeply comatose [Table 1].[30,31]
Treatment
Prompt initiation of antituberculosis treatment is the
cornerstone of treatment of TBM. In the intensive phase of
2 months, four antituberculosis drugs, rifampicin, isoniazid,
pyrazinamide, and ethambutol or streptomycin are given. In
the continuation phase of 7‑10 months, two drugs rifampicin
and isoniazid are continued. Corticosteroids are given to all
patients to minimize the host’s inflammatory damage.[32,33]
Treatment of hydrocephalus is generally medical, many rapidly
deteriorating patients may need surgical treatment.
Medical Management
Patients with communicating hydrocephalus are treated
medically. Steroids have been shown to reduce mortality in
all patients with TBM. Corticosteroids use in TBM is also
 Paliwal and Garg: Hydrocephalus in Tuberculous Meningitis ‑ Pearls and Nuances
Table  1: Modified Vellore grading for patients with
tuberculous meningitis and hydrocephalus
Grading Clinical features
I GCS 15
Headache, vomiting, fever ± neck stiffness
No neurological deficit
II GCS 15
Neurological deficit present
III GCS 9‑14
Neurological deficit may or may not be present
IV GCS 3‑8
Neurological deficit may or may not be present
GCS=Glasgow Coma Scale Score
associated with survival benefits and with a reduced incidence
of neurological sequelae.[33] Corticosteroids reduce vasogenic
edema and inflammation leading to relief in fever, headache,
and other signs of raised intracranial pressure.
Acetazolamide and diuretics are other drugs that are used in
communicating hydrocephalus because these drugs reduce
the production of CSF and improve interstitial edema. In
more severe cases, osmotic diuretics like mannitol and
hypertonic saline are indicated. Mannitol and hypertonic
saline are used as a bridging therapy before the surgical
option is contemplated. Acetazolamide and diuretics are
effective in controlling intracranial tension. There may
not be a reduction in ventricle size following medical
treatment, however, there may be a significant reduction in
the periventricular ooze. Schoeman and colleagues noted
that adjunctive medical therapy directed towards treatment
of hydrocephalus and increased intracranial pressure, does
affect mortality.[32]
Surgical Treatment
TBM patients with hydrocephalus, refractory to medical
treatment, surgical options are considered. CSF flow is
diverted surgically, so more CSF is accumulated in ventricles.
Surgical options include bedside external ventricular
drain, ventriculoperitoneal shunt, or endoscopic third
ventriculostomy. Very rarely, other methods, like suboccipital
decompression and craniotomy (for sequestered ventricles),
are needed.[26,34]
There are no clear‑cut indications for performing CSF diversion
procedures. All patients, with deteriorating sensorium,
progressive vision loss, and neuroimaging demonstrating
increasing ventriculomegaly despite medical treatment, may
need CSF diversion. Non‑communicating hydrocephalus,
usually, does not respond to medical treatment and should
always be treated surgically.[37] Patients clinically responding
to a trial of bedside external ventricular drainage, should be
subjected to ventriculoperitoneal shunt, or endoscopic third
ventriculostomy.[35]
Ventriculoperitoneal Shunt
A meta‑analysis comprising of 19 studies and 1038 patients
has tried to answer the questions regarding the outcome of
ventriculoperitoneal shunts in TBM.[36] The meta‑analysis noted
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S333
a good outcome in 58.3% of patients. The best outcome was
seen in patients with grade‑I TBM and worse outcome in TBM
patients with Vellore Grade‑IV disease. HIV‑positive patients
had a poorer outcome. Mortality was higher in HIV‑infected
TBM patients in comparison to HIV‑ negative patients (67%
versus 18%).
Shunt malfunctions are common and many patients require
shunt revision. Patients with very high CSF protein levels
are at high risk of shunt malfunction. Approximately 22%
of patients develop shunt‑related complications following
ventriculoperitoneal shunting.
Shunt block is the most common cause of shunt malfunction.
Other shunt related complications are shunt infection, shunt
erosion, shunt displacement, and development of peritoneal
cysts/loculations.[36]
Endoscopic Third Ventriculostomy
Endoscopic third ventriculostomy is an equally effective
alternative to ventriculoperitoneal shunt. Theoretically, it
can help get away with the fear of shunt obstruction. In a
meta‑analysis of studies that employed endoscopic third
ventriculostomy to treat hydrocephalus in patients with
TBM, eight studies with a pooled data from 174 patients were
studied.[37] The pooled success rate was 59%. The technical
failure rate was 5% and the complication rate was 15%.
Non‑communication hydrocephalus had a better odds ratio
for success after endoscopic third ventriculostomy.
Ventriculoperitoneal Shunt Versus Endoscopic Third
Ventriculostomy
The pooled success rates of ventriculoperitoneal shunt
and endoscopic third ventriculostomy are comparable.
However, the possibility of shunt malfunction in a large
number of patients after ventriculoperitoneal shunting, many
neurosurgeons prefer endoscopic third ventriculostomy.
On the contrary, endoscopic third ventriculostomy in TBM,
because of the presence of thick exudate at the floor of the
third ventricle, is difficult to perform. The presence of exudates
hiders identification of mammillary bodies, so, there is
difficulty in identifying the location to create a stoma.[35] Risk
of failure of endoscopic third ventriculostomy is high in the
immediate post‑operative period, with time the risk of failure
becomes progressively lesser.[38]
Figaji and Fieggen in their review agued, that endoscopic
third ventriculostomy by an inexperienced surgeon is a
difficult procedure to perform. They further argued that
endoscopic third ventriculostomy converts non‑communicating
hydrocephalus into communicating hydrocephalus because
there is CSF malabsorption because of obstruction at the level
of basal cisterns. Patients continue to require medical treatment.
Repeated lumbar puncture may also be required to control
raised intracranial pressure.[35]
There are no clear guidelines available suggesting a choice
between ventriculoperitoneal shunt and endoscopic third
ventriculostomy. Choices are based on the individual
preference and expertise of neurosurgeons.
 Paliwal and Garg: Hydrocephalus in Tuberculous Meningitis ‑ Pearls and Nuances
Conclusion
Hydrocephalus is seen in up to 80% of patients with tuberculous
meningitis. Hydrocephalus is much more commonly reported
in children with TBM. Thick basal exudates are responsible for
obstructing CSF flow resulting either in non‑communicating
hydrocephalus or more frequent communicating hydrocephalus.
Increased frequency of seizures, cranial nerve palsies, vision
loss, papilledema, extensor plantar response, and deteriorating
consciousness is noted in TBM patients with progressive
ventriculomegaly. Proportionally dilated fourth ventricle,
on neuroimaging, suggests the possibility of communicating
hydrocephalus. Air pneumoencephalogram is an ideal method
to differentiate between two types of hydrocephalus. Air
pneumoencephalogram is not routinely performed. Patients
with communicating hydrocephalus respond to medical
therapy with corticosteroids, acetazolamide, or diuretics.
Patients with non‑communicating hydrocephalus require a CSF
diversion procedure, ventriculoperitoneal shunt, or endoscopic
third ventriculostomy, to be performed. In many cases, CSF
diversion is believed to be life‑saving in short term. Long‑ the
impact of CSF diversion procedures on the overall prognosis
of TBM is not known. The exact timing, of CSF diversion
procedures, in the course of TBM, is another important question
that needs an answer. Randomized‑controlled trials with longer
follow up are needed to answer these pertinent questions.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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36. Rizvi I, Garg RK, Malhotra HS, Kumar N, Sharma E, Srivastava C,
et al. Ventriculo‑peritoneal shunt surgery for tuberculous meningitis.
A systemic review. J Neurol Sci 2017;375:255‑63.
37. Legaspi GD, Espiritu AI, Omar AT 2nd. Success and complication
rates of endoscopic third ventriculostomy for tuberculous
meningitis: A systematic review and meta‑analysis. Neurosurg Rev
2021;44:2201‑9.
38. Goyal P, Srivastava C, Ojha BK, Singh SK, Chandra A, Garg RK,
et al. A randomized study of ventriculoperitoneal shunt versus
endoscopic third ventriculostomy for the management of tubercular
meningitis with hydrocephalus. Childs Nerv Syst 2014;30:851‑7.

Neurology India | Volume 69 | Supplement 2 | November-December 2021 S335

 Review Article

Access this article online

Quick Response Code:
Diagnostic Nuances and Surgical
Management of Arrested
Hydrocephalus
Manas K Panigrahi, Sandhya Kodali, Y B V K Chandrsekhar, Sudhindra Vooturi1
Website:
www.neurologyindia.com

DOI: Abstract:
10.4103/0028-3886.332262
Hydrocephalus is characterized by the increased volume of cerebrospinal fluid (CSF) with enlarged cerebral
ventricles. In nearly 50% of the patients, if left untreated, the balance between CSF production and absorption
is achieved, resulting in arrested hydrocephalus  (AH). However, 15% of them who are diagnosed as
arrested can progress over a period of time. Importantly, a large fraction of patients with hydrocephalus in
India, may not have access to tertiary level care. Therefore, both progressive hydrocephalus and insidious
progression of AH with related mortality and morbidity could be higher in India. The pathophysiology behind
AH and insidious progression of AH are poorly established. Unfortunately, there are no established clinical
or radiological parameters identifying or predicting AH from progressive hydrocephalous. Diagnosis is often
based on a combination of neurological, psychometric, and magnetic resonance imaging  (MRI) findings.
Invasive monitoring of intracranial pressure (ICP) and telemetric ICP measurement is increasingly helping
surgeons to detect insidious progressive AH in the early stages. In patients with AH, surgery may not be always
necessary and a conservative approach is often adopted. On the contrary, AH that becomes progressive may
require intervention. Surgical intervention should not be delayed and endoscopic third ventriculostomy (ETV)
is preferable over shunt placement. Importantly, comprehensive counseling and the appropriate selection of
patients are pivotal in improving outcomes and reducing complications.
Key Words:
Arrested hydrocephalus, endoscopic third ventriculostomy, flow‑diversion, intracranial pressure monitoring,
shunts

Key Message:
In patients with AH, surgery may not be always necessary. However, AH that becomes progressive may
require intervention and ETV is preferable over shunt placement.

H ydrocephalus is characterized by increased

volume of cerebrospinal fluid (CSF)
with enlarged cerebral ventricles and/or the
This reported natural history of hydrocephalus,[1]
predominantly from western countries, may
differ from the Indian scenario.[4] In developing
subarachnoid space. In addition, in children, countries like India, even among those who
hydrocephalus may also be associated with afford tertiary care, cost‑effectiveness often
increased intracranial pressure (ICP). In nearly leads to a clinical decision, thus leading to
Departments of 50% of the patients, after the initial progression, cost‑effective innovations in neurosurgery.[4]
Neurosurgery the balance between CSF production and Importantly, a large fraction of patients with
and 1Neurology, absorption is achieved if left untreated, thus hydrocephalus in India, may not have access to
Krishna Institute of halting the progression of hydrocephalus tertiary level care. Therefore, both progressive
Medical Sciences, and ICP returns to normal values called hydrocephalus and insidious progression of AH
Secunderabad, arrested hydrocephalus (AH) or compensated with related mortality and morbidity could be
Telangana, India hydrocephalus.[1,2] Furthermore, hydrocephalus higher in India.
without signs of acute raised ICP, or progressive
Address for neurological and psychological deficiencies is Unfortunately, there are no established clinical or
correspondence: often referred to as AH. However, an AH has radiological parameters identifying or predicting
Dr. Manas K Panigrahi,
been reported to become insidiously progressive AH from progressive hydrocephalous. In patients
Department of
Neurosurgery, hydrocephalus in nearly 15% of the children.[1‑3]
Krishna Institute of How to cite this article: Panigrahi MK, Kodali S,
Medical Sciences, This is an open access journal, and articles are distributed under the terms Chandrsekhar YB, Vooturi S. Diagnostic Nuances
1‑8‑31/1, Ministers of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 and Surgical Management of Arrested Hydrocephalus.
Road, Secunderabad, License, which allows others to remix, tweak, and build upon the work Neurol India 2021;69:S336-41.
Telangana, India non‑commercially, as long as appropriate credit is given and the new
creations are licensed under the identical terms. Submitted: 24‑Jun‑2021 Accepted: 27‑Sep‑2021
E‑mail: manasp1966@ Published: 11-Dec-2021
gmail.com For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com

S336 © 2021 Neurology India, Neurological Society of India | Published by Wolters Kluwer - Medknow
 Panigrahi, et al.: Arrested hydrocephalus: diagnosis and management
with AH, surgery (Endoscopic third ventriculostomy, Figure 1)
may not be always necessary and a conservative approach is
often adopted. On the contrary, AH that becomes progressive
may require intervention. The pathophysiology behind AH and
insidious progression of AH are poorly established. Numerous
studies have proposed various resorption pathways that aid
in achieving a balance between production and absorption of
the CSF.[5] Unfortunately, the review of pathophysiology of
AH is not the scope of this review. In this article, we review
the literature on AH and discuss few interesting case studies of
AH. Furthermore, we propose an approach for the management
of AH.
Clinical   Presentation
Clinical presentation of children with AH, although often
but not always, include symptoms associated with raised
ICP, like macrocephaly (almost always the first sign), frontal
bossing, headache, altered consciousness, irritability, nausea,
vomiting, or papilledema. Family history for macrocephaly
may be observed in few patients. However, in an AH that may
begin to progress, clinical symptoms of raised ICP may also
be associated with neurological signs such as dystonia, ataxia,
tremor, and gross motor delay. Few children may additionally
demonstrate “regression” of neuropsychological and physical
milestones. Ophthalmological evaluation by direct and indirect
fundoscopy may reveal bulging or atrophied optic discs,
papilledema (intracranial hypertension).[6]
Radiological evaluation
Magnetic resonance imaging (MRI) has been the mainstay of
radiological evaluation of hydrocephalus. Particularly, the size
and shape of the cerebral ventricles and subarachnoid space
form the crux of the direct and indirect signs of raised ICP. In
addition, vascular or parenchymal signs on MRI, associated
with the hydrocephalus, especially in AH are also important.
Furthermore, quantification of ventricular size is often done
applying the frontal and occipital horn ratio (FOHR) on MRI.[7]
This quantification also helps in scrutinizing the change over
time. Radiological evaluation is often advised in patients with
persistent, deteriorating, or new neurological abnormalities
with or without regression of developmental milestones.
Features on MRI in patients with AH are often suggestive
of panventriculomegaly or enlargement of one or two of the
ventricles that have not worsened over time in three patients.
However, in patients with insidious progressive hydrocephalus,
dilatation of the ventricles (one of the ventricles) may be
associated with widening of the extra‑axial subarachnoid space.
Other radiological features include depressed third ventricular
floor [Figure  2] with arachnoid thickening, generalized thinning
of the walls of the corpus callosum [Figure 3], periventricular
sunray appearance [Figure 4], straightening of the anterior
wall of the third ventricular, and enlargement of the recesses.
In addition, the elevation of the cerebellum and/or dilatation
of the basal cisterns with/without the cisterna magna may
be present. It is also suggested to observe for any arachnoid
cysts blocking the CSF too. Moreover, measurement of the
optic nerve sheath diameter on MRI is helpful in the long‑term
evaluation.[8,9]
Recent advances in radiology and imaging are increasingly
helping to differentiate between AH and insidious progressive
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S337
hydrocephalus. Two such MRI markers include, apparent
diffusion coefficient  (ADC) and cerebral blood flow  (CBF)
20 wherein elevated periventricular ADC and decreased
CBF may be independently suggestive of progressive
hydrocephalus.[10,11] Moreover, three‑dimensional sampling
perfection with application optimized contrasts using
different flip‑angle evolution  (3D‑SPACE) techniques, of
MRI is highly resistant to artifacts. It has been recently
reported that T2‑weighted  (T2W) 3D‑SPACE with variant
flip‑angle mode (VFAM) imaging allows accurate evaluation
of the hydrocephalus patients during both preoperative and
postoperative periods.[12] Furthermore, the 3D‑SPACE sequence
in hydrocephalus helps to differentiate obstructive from
communicating hydrocephalus, thereby helping to improve
patient selection for endoscopic procedures.[13]
Phase‑contrast MRI,[14] due to its bipolar gradient, when
placed after the radiofrequency pulse and before data
collection during echo time provides a qualitative and
quantitative assessment of CSF flow. In patients post VP
shunt for hydrocephalus, the patency of shunt can be
evaluated with PC‑MRI. Not only in VP Shunts, but PC‑MRI
is also useful in post endoscopic third ventriculostomy, to
quantify the patency of the opening and the restoration
of the pulsatile CSF. However, findings on phase‑contrast
MRI in turbulent CSF flow are vulnerable to inconsistencies.
Contrast‑material‑enhanced MR cisternography (CE‑MRC)
may provide additional data to diagnose NPH, especially in
communicating hydrocephalus. It may also help in predicting
treatment response in patients undergoing intervention for
hydrocephalus. One of the major drawbacks of CE‑MRC, it
that it is an invasive procedure and dependent on the expertise
of the radiologist.[15]
Intracranial pressure (ICP) monitoring
Invasive monitoring of ICP helps to distinguish various
hydrocephalus. In active hydrocephalus, the mean ICP
is more than 12 mmHg whereas AH has a mean ICP
less than or equal to 12, compensated hydrocephalus
has an ICP similar to AH but with coexisting A and B
waves. [16] However, in patients with normal ICP and
baseline, long‑term monitoring of ICP helps identify
asymptomatic cases with temporary, fluctuant, but repeated
pressure elevations, which may be resultant of insidious
progressive hydrocephalus.[17] Importantly, in patients with
neurodevelopmental abnormalities like spina bifida, assumed
to have AH, continuous ICP monitoring revealed active
hydrocephalus in 58% and compensated hydrocephalus in
32%. Surprisingly, only 10% of these children had AH.[16] This
emphasizes the role of continuous ICP monitoring, especially
in patients with mental retardation, low IQ, or regression of
neuropsychometric milestones. Since ICP is measured by
invasive procedures, chances of infection and hemorrhage
are inherent. Therefore, in most patients, neurological signs
and progression on radiological markers should be sufficient
enough for decision markers. However, in patients with
low or regressed psychometric performance, ICP can be a
diagnostic tool of choice. Encouragingly, newly introduced
telemetric ICP recording technology allows for continuous
repeated measurements of ICP at relatively lower risk.[18]
Although only a few case reports have reported the use of
telemetric ICP; the future is promising.
 Panigrahi, et al.: Arrested hydrocephalus: diagnosis and management
Management
Accurate treatment strategy depends greatly on appropriate
selection of patients since enlarged ventricle(s) is not
the only criteria, for optimal management plan. More
often than not, diagnosis of insidious progressive
hydrocephalus is mostly through exclusion on diagnostic
tests, serial clinical, and radiological workup is mandatory.
Importantly, a comprehensive assessment should also
include neuropsychometry and ophthalmological evaluation.
Monitoring of the ICP is necessary to rule out any little doubt.
Table 1, summarizes the proposed system of scoring and
management of arrested and progressive hydrocephalus. It is
of utmost importance to remember that the proven necessity of
intervention arises, early intervention yields a better outcome.
Conservative management
In patients, where conservative management is opted for,
existing literature suggests “active imaging surveillance
along with neurological, psychometric, and ophthalmological
assessment at every 2 to 3 months, then at 6 to 9 months,
followed by a yearly  visit”.[7]
Shunts[19]
Flow diversion using shunts is often done by a
ventriculoatrial  (VA), ventriculoperitoneal  (VP), and
lumbo‑peritoneal (LP). It is very important for the surgeon to
note that rapid or over drainage may lead to subdural effusions
and hematomas with resultant neurological deterioration thus
requiring surgery. To avoid these complications, surgeons
across the globe are increasingly using programmable valves
with antisiphon devices. Despite adequate precautions,
follow‑up studies have reported shunt malfunction in up to
one‑fourth of subdural hematomas in up to 10% of children,[20,21]
requiring ventriculostomy. Therefore, patients and their
caregivers should be adequately counseled about life‑long
shunt‑related risks, especially in children.
Endoscopic third ventriculostomy (ETV)[19]
The latest advancements in and increasing use of endoscopy
in neurosurgery, makes ETV a treatment of choice, given that
AH has extreme venticulomegaly. The steps of ETV involve a
small curvilinear incision just above coronal suture, placement
of Burr hole, initial ventricular cannulation, and performing
a ventriculostomy on the floor of the third ventricle using
endoscopic spreading forceps. LASER‑assisted ETV is used
when the floor of the third ventricle is thickened. In this
procedure, under endoscopic guidance, multiple perforations
to the floor of the ventricle are done using a laser [Figure 1].
Endoscopic third ventriculostomy  (ETV) has become
an increasingly popular method of treating arrested
hydrocephalus for several reasons. First, ETV avoids or
delays shunt implantation and its associated complications.
Table 1: Proposed scoring system to help in formulating management strategy (SMAP ‑ Scoring and
Management of Arrested and Progressive Hydrocephalus)
Neurological/Clinical Evaluation Neurodevelopmental Evaluation
0 No deficits No deficits
1 Occasional symptoms of raised ICP
2 Neurological deterioration Regression of milestones
3 Raised ICP on invasive/telemetry monitoring
A cumulative score of <3 should be considered for conservative management, whereas a cumulative score ≥3 should be referred for surgical intervention at the earliest
S338 Neurology India | Volume 69 | Supplement 2 | November-December 2021
Second, advancements in endoscope technology have made
the procedure more accessible to neurosurgeons. Finally,
patients with arrested hydrocephalus can have extreme
ventriculomegaly, which is favorable for endoscopic
procedures. Recent literature has proven that ETV improves
neuropsychiatric function in nearly 70% of the children and
headache control in 70% to 100% of children at short‑ and
long‑term follow‑up.[5,19‑22]
However, it is important to realize that ETV carries a risk of
intraoperative and perioperative hemorrhage requiring shut
placement. Therefore, it is reasonable to attempt ETV as an
initial treatment and reserve shunt placement in the event of
ETV failure due to the risk of the device malfunction, foreign
body implantation, and over drainage associated with shunts.
Figure 2 summarizes the probable flow chart for strategizing
the management of hydrocephalus.
Prognosis
When left untreated, the mortality in progressive hydrocephalus
is approximately 80%. Among the remaining 20%, two‑thirds
of them develop cognitive and intellectual deficits with
an associated physical disability.[23] Among patients who
opt to undergo intervention, the outcome is influenced by
clinical (etiology, presurgical deficits, seizures, and ventriculitis),
radiological (degree of ventriculomegaly and topography of
ventricles), and perioperative factors (age at surgery, shunt
potency, and surgery‑related complications). [4] Among
children, it is generally accepted that ideally CSF diversion
should be done before 6 months of age. [4,24] Interestingly,
children intervened after 18 months of age, developed higher
perioperative complications like subdural hematomas, and
reported poor intellectual outcomes.[23] Perhaps, the cortical
Figure 1: Intraoperative image of endoscopic third ventriculostomy depicting
thickned floor of the third ventricle and the tip of the LASER
Radiological Evaluation
No progression/No new signs
Ventriculomegaly only
Ventriculomegaly and signs of raised ICP
 Panigrahi, et al.: Arrested hydrocephalus: diagnosis and management

Figure 2: Flow chart for strategizing management in arrested and progressive hydrocephalus

Figure 3: Magnetic resonance imaging illustrating thinning or corpus callosum suggestive of long‑term compression but without signs of raised intracranial pressure

with shunt‑dependent hydrocephalus may present some

temporary, mild neurological, and cognitive disturbances
till adulthood in comparison with the normal population.[16]
Potential risks of hydrocephalus decompensation and sudden
death should also be counseled to the patient who opts for
intervention.[7,16]

Figure 4: In a suspected case of hydrocephalus with regression of milestones over
the last 3 months. MRI revealed ventriculomegaly with aqueductal stenosis and
floor of third ventricle was bulging downward
Illustrative cases
Case study 1
A 1‑year‑old patient, a known case of hydrocephalus, was
referred to our center for advice regarding management.
Neuropsychometric evaluation was normal. MRI [Figure 3]
had ventriculomegaly without any signs of raised ICP. The
patient was advised for conservative management with regular
follow‑up.

mantle loses its ability to reconstitute with advancing age in Case study 2
children.[4,24] A suspected case of hydrocephalus with regression of milestones
over the past 3 months. MRI revealed ventriculomegaly
Patients with AH have normal intelligence with scholastic with aqueductal stenosis and the floor of the third ventricle
performance equal to age‑matched peers. However, patients was bulging downward [Figure 4]. Endoscopic third
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S339
 Panigrahi, et al.: Arrested hydrocephalus: diagnosis and management
ventriculostomy was done and the child had started attaining
his milestones at the latest follow‑up.
Case Study 3
A 14‑year‑old child presented with a headache with an
insidious onset but was progressing gradually over the last
6 months. MRI [Figure 5] revealed dilated lateral ventricle and
third ventricle with periventricular seepage along the third
ventricle floor and bulging inferiorly and a normal fourth
ventricle. The patient underwent an ETV with a good outcome.
Case study 4
An 8‑year‑old child presented poor scholastic performance
over the last 1 year. Magnetic resonance imaging revealed a
sun‑ray appearance along the corpus callosum [Figure 6]. The
child underwent an ETV, intraoperative and postoperative
recovery was uneventful.
Conclusion
In patients with AH, predicting insidious progression is a
challenge. Therefore, meticulous clinical and radiological
monitoring is often advised. A conservative approach is the
choice of treatment in patients with AH established after clinical
and radiological evaluation. Otherwise, surgical intervention
should not be delayed and ETV is preferable over shunt
placement. Importantly, comprehensive counseling and the
appropriate selection of patients are pivotal in improving
outcomes and reducing complications.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
Figure 5: Magnetic resonance imaging reveals dilated lateral ventricle and third
ventricle with periventricular seepage along the third ventricle floor and bulging
inferiorly
Figure 6: Magnetic resonance imaging depicting sun‑ray spicule appearance in
the corpus callosum suggesting a raise in intracranial pressure progression of the
hydrocephalus
S340 Neurology India | Volume 69 | Supplement 2 | November-December 2021
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2. Schick RW, Matson DD. What is arrested hydrocephalus? J Pediatr
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4. Venkataramana  NK. Hydrocephalus Indian scenario ‑ A review.
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6. Rudolph D, Sterker I, Graefe G, Till H, Ulrich A, Geyer C. Visual
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8. McAuley D, Paterson A, Sweeney L. Optic nerve sheath ultrasound
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9. Singhal A, Yang MM, Sargent MA, Cochrane DD. Does optic nerve
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10. Leliefeld PH, Gooskens RH, Braun KP, Ramos LM, Uiterwaal CS,
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11. Leliefeld  PH, Gooskens  RH, Vincken  KL, Ramos  LM,
van der Grond J, Tulleken CA, et al. Magnetic resonance imaging
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12. Algin  O. Evaluation of hydrocephalus patients with 3D‑SPACE
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15. Kartal  MG, Algin  O. Evaluation of hydrocephalus and other
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16. Mataro  M, Poca  MA, Sahuquillo  J, Cuxart  A, Iborra  J,
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Neurology India | Volume 69 | Supplement 2 | November-December 2021 S341

 Review Article

Access this article online

Quick Response Code:
Hydrocephalus Associated with
Posterior Fossa Tumors: How to
Manage Effectively?
Natarajan Muthukumar
Website:
www.neurologyindia.com

DOI: Abstract:
10.4103/0028-3886.332260
Background: Hydrocephalus associated with posterior fossa tumor (PFT) is a common neurosurgical problem,
the management of which is still controversial.
Aim: To provide an overview of the advantages and limitations of different management strategies for
hydrocephalus associated with PFT both before and after resection of these tumors.
Methods: Structured review of the literature on the management of hydrocephalus in PFT both in children
and adults.
Results: The incidence of hydrocephalus associated with PFT at the time of presentation is more in
children (70–90%) than adults (10–21%). This difference is maintained for hydrocephalus after the resection
of PFT (~30% for children and 1.2–6.9% for adults). Preresection hydrocephalus is obstructive while emerging
evidence in the literature suggests that postresection hydrocephalus may have a communicating component.
The treatment of preresection hydrocephalus associated with PFT has undergone a paradigm shift in the past
two decades. Preoperative Cerebrospinal Fluid (CSF) diversion is less commonly used except when required
by the clinical condition of the patient. Preresection hydrocephalus may be treated by steroid use and early
tumor removal, perioperative use of external ventricular drainage, or endoscopic third ventriculostomy in
selected patients. Various prediction scales are available to assess the risk of postresection hydrocephalus
in PFT. Certain histological tumor types and molecular phenotypes of PFT are more commonly associated
with hydrocephalus. CSF diversion through endoscopic third ventriculostomy or ventriculoperitoneal shunts
remains the management strategies for postresection hydrocephalus. The failure rates and the time‑to‑failure
of both endoscopic third ventriculostomy and CSF shunts in PFT are variable and surgeons should be aware
of these while taking management decisions.
Conclusions: Hydrocephalus associated with PFT affects the quality of life of patients with such lesions.
Routine preoperative CSF diversion is not necessary for the vast majority of patients with posterior fossa
tumor‑related hydrocephalus. A high index of suspicion and aggressive surveillance is required for the early
identification and appropriate management of postresection hydrocephalus. Future studies are needed to
address several unanswered questions pertaining to the management of this condition.
Key Words:
Complications, endoscopic third ventriculostomy, external ventricular drainage, hydrocephalus, posterior
fossa tumor, ventriculoperitoneal shunts

Key Message:
Preresection and postresection hydrocephalus are more common in children than in adults with PFT. The
current consensus in the literature is to avoid the preresection CSF diversion except in special circumstances.
External ventricular drainage, or occasionally, endoscopic third ventriculostomy is the preferred method of
preresection CSF diversion. A high index of suspicion and appropriate surveillance is required for early
identification of postresection hydrocephalus which can be managed by endoscopic third ventriculostomy or
occasionally by shunts. It is possible to reasonably predict the occurrence of postresection hydrocephalus
Department of
using the prediction scales outlined in the text.
Neurosurgery,
Devadoss Hospital,
Madurai ‑ 625 020,
Tamil Nadu, India M anaging hydrocephalus due to posterior
fossa tumors (PFTs) presents a complex and
challenging problem and neurosurgeons have
over the years. For decades, CSF shunts were
considered to be the gold standard. However,
improved understanding of the disease process
Address for adopted various modes to treat this condition as well as the recent advances have caused
correspondence:
Dr. Natarajan Muthukumar, This is an open access journal, and articles are distributed under the terms How to cite this article: Muthukumar N. Hydrocephalus
Muruganagam, 138, Anna of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 Associated with Posterior Fossa Tumors: How to
Nagar, Madurai ‑ 625 020, License, which allows others to remix, tweak, and build upon the work Manage Effectively? Neurol India 2021;69:S342-9.
Tamil Nadu, India. non‑commercially, as long as appropriate credit is given and the new
creations are licensed under the identical terms. Submitted: 22‑Jun‑2021 Revised: 31-Jul-2021
E‑mail: drnmuthukumar@ Accepted: 13-Sep-2021 Published: 11-Dec-2021
yahoo.com For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com

S342 © 2021 Neurology India, Neurological Society of India | Published by Wolters Kluwer - Medknow
 Muthukumar: Hydrocephalus associated with posterior fossa tumors
a paradigm shift in the management of PFT‑associated
hydrocephalus. The following discussion will examine the
current evidence in the literature about the management of
hydrocephalus associated with PFT. In this discussion, PFTs
do not include tectal and pineal region tumors.
Incidence and Importance of Hydrocephalus in
Posterior Fossa Tumors
Hydrocephalus significantly impacts the quality of life in
children with PFT.[1] The incidence of hydrocephalus in patients
with PFT varies between children and adults. In children, the
incidence of hydrocephalus at presentation is higher than in
adults. In adults, the incidence varies from 10 to 21.4%[2,3] whereas
in children it is between 70 and 90%[4‑9]. The exact reason for this
higher incidence of hydrocephalus in children with PFT is not
known but one study attributed it to the larger median lesion
size.[3] The incidence of hydrocephalus after resection of PFT is
also higher in children (37.5%) than in adults (6.9%).[2,3]
Management Options for Hydrocephalus in PFT
The obstructive nature of the hydrocephalus that is associated
with PFT makes CSF diversion a rapid way to reduce the
intracranial pressure. These options include the preoperative
use of corticosteroids, emergency tumor removal, or CSF
diversion procedures. Several authors advocate the short‑term
use of corticosteroids followed by early surgical removal of the
tumor. However, in clinical practice, this is not always feasible
either because of the clinical condition of the patient or the
local organization of the neurosurgical unit. In such cases, CSF
diversion procedures are viable options. These CSF diversion
procedures can be either internal (ETV) or external (external
ventricular drainage [EVD], Ommaya reservoir, shunt). The
following are the various surgical options available to manage
hydrocephalus in PFT:
1. Extrathecal CSF shunts
2. Endoscopic third ventriculostomy (ETV)
3. EVD
4. External CSF reservoirs or ventricular access devices
Each of these management options has several advantages and
limitations as discussed below.
Extrathecal CSF Shunts before the Resection of PFT
Historically, preresection CSF shunting was shown to
dramatically reduce the mortality and morbidity associated
with PFT surgery in both children and adults.[4,6,7] However,
this procedure has several advantages and disadvantages
Advantages:
• Preoperative CSF shunting leads to immediate symptomatic
improvement[4,6,7]
• Smooth postoperative recovery,
• Decreased mortality (12.8% without shunting vs. 3.7% with
shunting[6]
• Significant (>80%) resolution of papilledema[6]
• Bulging of the posterior fossa dura decreased from 30%
without shunting to 8% with shunting[6,7]
• Decreased rate of postoperative CSF leak and
pseudomeningocele[7]
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S343
The disadvantages include:
• CSF shunting commits the patient and the surgeon to a
lifetime of vigilance as many of these patients become shunt
dependent[10,11]
• Shunts are also notorious for their failure rates which can
be as high as 38% during the first 2 years of surgery.[10]
• Shunt complications like infection, hardware breakage,
visceral perforation, etc., are well‑known.
• Shunt infections are independent predictors of death in
pediatric patients[12]
• Intratumoral hemorrhage or upward herniation can occur
in 2.8% of the patients who undergo VPS for PFT.[13]
• Rarely, tumor cells can metastasize through the shunt
tube[14]
As the outcomes of patients with PFT have improved over the
years, postoperative shunt dependency and the complications
associated with it are becoming increasingly important as
they affect the quality of life.[10] In the past two decades, most
neurosurgeons have abandoned preoperative VPS for PFT.
However, as noted later in the discussion, there are still certain
occasions where VPS might have a role in PFT‑associated
hydrocephalus.
External Ventricular Drainage
Placement of an EVD either preoperatively or intraoperatively
in patients with PFT is a common procedure that is practiced
worldwide.[15]
Advantages of EVD:
• Life‑saving procedure in patients who present with
markedly elevated Intracranial Pressure (ICP) and altered
sensorium[16,17]
• Provides easy CSF diversion[16,17]
• Controlled drainage of CSF is possible, thereby, decreasing
the incidence of upward herniation and intratumoral
hemorrhage[15]
• If performed during surgery, it helps to remove the blood
and tumor debris in the ventricles, and thereby, decreases
the chance of Post-Resection Hydrocephalus (PRH)
• In the postoperative period, it can help monitor ICP after the
resection, and thus, help decide which patient will require
postresection CSF diversion[18,19]
• As most patients with PFT  (~ 70%) do not develop
hydrocephalus after tumor resection, EVD helps to avoid
the complications of preresection CSF diversion procedures
like VPS and ETV.
Disadvantages:
• The EVD infection rate may vary from 4.9 to 17% depending
upon the duration of the drainage.[20] However, this infection
rate is reduced by the use of antibiotic‑impregnated
ventricular catheters[21]
• The EVD use is associated with an increased incidence of
postresection hydrocephalus  (PRH) as shown by many
studies[11,22,23]
• A longer duration of EVD placement is associated not only
with increased infection rates but also with an increased
chance of PRH[24,25]
• There is a small risk of upward herniation following
preoperative EVD placement[2,13,26‑29]
 Muthukumar: Hydrocephalus associated with posterior fossa tumors
Ventricular Access Devices (Ommaya/Rickham
Reservoir)
There are a few studies in the literature that deal with the usage
of ventricular access devices for the perioperative management
of hydrocephalus associated with PFT.[30,31] Jiang and colleagues
used an external ventricular access device for hydrocephalus
management in 48 children with PFT and found that no patient
required a postoperative shunt and the infection rate was
19% which responded to conventional antibiotic therapy.[30]
Schmid and Seiler used an external ventricular access device
for the management of 61 patients with PFT (38 adults and 23
children). With this procedure, 100% of the adults and 83% of
the children were shunt‑free during the follow‑up period and
the infection rate was 4.9%.[31]
Endoscopic Third Ventriculostomy
In the past two decades, ETV has become a popular option for
the treatment of hydrocephalus associated with PFT both before
and after tumor resection.[32,33] However, controversy still exists
regarding the role of ETV in the management of PFT‑associated
hydrocephalus. There are several unanswered questions
regarding the changing role of ETV in this situation. The
tumor removal following ETV should augment ETV success
by opening the natural CSF passage, and thereby, establishing
a pressure gradient across the stoma.[2] However, the tumor
surgery can cause bleeding within the ventricular system and
can lead to the closure of the stoma.[2] The ETV in posterior
fossa tumors should be theoretically more complicated because
the PFT should reduce the size of the prepontine cisterns and
make the procedure more difficult.[2,10] However, this has not
been found to be true in practice.[10]
The advantages of a preresection ETV are several.
• It allows rapid control of the increased ICP in 44–96% of
the cases[27,28,34]
• During tumor resection, the dura is lax, and therefore, the
need for intraoperative EVD is avoided[10,32]
• The need for postoperative external CSF drain and its
associated complications are avoided
• Avoids the placement of an extrathecal CSF shunt with its
associated complications
• Tumor removal can be scheduled electively allowing time
for adequate preoperative evaluation[34]
• Reduces the incidence of postoperative CSF leak and
pseudomeningocele[32,35]
• In the cases where neoadjuvant chemotherapy is planned
before resection, the ETV and subsequent control of
hydrocephalus allows time for such treatment[36,37]
• It is known to decrease the incidence of PRH[32,38]
• ETV is known to offer a long‑term treatment survival
advantage compared to a VP shunt[39,40]
• Preresection ETV has the potential to decrease the duration
of EVD postoperatively, and thus, the length of stay in the
ICU.[38]
• Preresection ETV may be an option in those patients
who are at a “high risk” for the development of PRH (as
discussed later)
• The performance of an ETV requires only basic and not
extended skills in neuroendoscopy, and therefore, can be
more widely adopted
S344 Neurology India | Volume 69 | Supplement 2 | November-December 2021
The disadvantages of preresection ETV are as follows:
• Only  ~30% of the patients have PRH, and therefore,
performing ETV in every patient preoperatively exposes
70% of the patients to an unnecessary surgical procedure.[41,42]
• Even though ETV is generally a safe procedure, it is
not entirely without complications. A meta‑analysis of
2,884  patients showed a complication rate of 8.5% with
permanent morbidity of 2.4%, mortality of 0.21%, and
delayed “sudden death” rate of 0.07%.[43]
• There is a risk of closure of the stoma of ETV done
preoperatively by the blood and tumor debris in the
ventricles after tumor resection necessitating a redo
procedure or a shunt[27,28]
• ETV failure is high in patients with CSF metastases at the
time of presentation[28,44]
Surprisingly, as in the children, in the adults also, there was a
demonstrable decrease in the need for postresection shunting
after preresection ETV.[27] However, there are very few studies
in the adult population that deal with this issue.
Comparison of ETV and VPS in Tumor‑Related
Hydrocephalus
It is important to know the long‑term durability of ETV
versus VPS in patients with PFT as the disease (PFT) with
its intrinsic survival‑limiting nature makes the question of
treatment durability very crucial.[26] Sherrod and colleagues
specifically studied the success and complication rates
of ETV in tumor‑related hydrocephalus by a pooled
meta‑analysis.[45] They found a failure rate of 18.3% with the
failure rates being almost the same between ETV and VPS with
a lower risk of infection in those patients undergoing ETV.
There is considerable controversy in the literature regarding
the time‑to‑failure between ETV and VPS. Dewan et al.[26]
noted a shorter time‑to‑failure for ETV than for VPS whereas
El‑Ghandour did not find a significant difference.[10] Dewan
et al.[26] conducted a systematic review of 408 patients to study
the durability of ETV versus VPS and found that the cumulative
failure rates were not significantly different between ETV and
VPS; however, there was a difference in the time‑to‑failure—the
ETV failure often occurred at a median of 1 month whereas
the VPS failure occurred at a median of 4 months. They also
found a statistically significant increase in the complication
rates in the VPS group (VPS 31%, ETV 17%). Kulkarni et al.[40]
compared the outcomes of ETV versus VPS in 1,200 patients
of whom 18% had tumor‑related hydrocephalus. They found
a 20% higher early failure rate in the ETV group relative to
the VPS group. However, over time, the risk of ETV failure
became lower than that of VPS indicating that the treatment
advantage of ETV is only seen beyond the early postoperative
period. The importance of this early failure of ETV in this
patient population will become evident later in this discussion.
Does Tumor Histology Influence the Success Rates
of ETV and VPS?
Schneider et al. [46] studied 28  patients with persistent
hydrocephalus following medulloblastoma resection—no
patients with a VPS required early reintervention whereas four
of the five patients in ETV had to be converted to VPS, thus,
 Muthukumar: Hydrocephalus associated with posterior fossa tumors
producing a success rate of 100% for VPS and 20% for ETV.[46]
This has therapeutic implications, viz. when a patient with
medulloblastoma with metastases develops hydrocephalus
postoperatively, VPS would be a better option than ETV as ETV
has a higher early failure rate, and a redo ETV might interfere
with the craniospinal irradiation/chemotherapy and limit the
quality of life of such a patient with poor long‑term survival.
As suggested by Dewan et al.,[26] VPS may be a better option
for children with aggressive tumors and limited survival and
ETV can be resorted to in those patients with low‑grade lesions.
Future studies should address these issues.
Which is the Best CSF Diversion Procedure for
Pediatric Patients with Metastatic Posterior Fossa
Tumors at Presentation?
Metastases at the time of presentation are not infrequent in
patients with newly diagnosed pediatric PFT and range from
7 to 17%[47] and may reach up to 30% in the newly diagnosed
medulloblastoma.[46] These patients require a different type
of care which may include early chemotherapy protocols,
either neoadjuvant or immediate postoperative.[37,47] Given the
limited survival period of these patients and the relatively high
incidence of hydrocephalus at presentation,[37] it is important to
know the success rates of different CSF diversion procedures
in this situation. In a landmark study, Dufour and colleagues
studied 29 children who presented with either macroscopic
metastases at the time of presentation or were found to have
metastatic cells in the CSF later.[47] They compared the failure
rates of VPS, ETV, and EVD in this setting. They found that
ETV had a failure rate of 55%, EVD had a failure rate of 57%,
while no failures occurred in the VPS group. They also noted
that the patients in the VPS group had a much earlier oncologic
treatment when compared to the other two groups.[47] This
study clearly highlights that ETV and EVD have high failure
rates in the pediatric PFT patients who have metastases and in
these subsets of patients, VPS is a better option.
Postresection Hydrocephalus (PRH)
PRH can be either early or late; early hydrocephalus is
often due to tumor‑related or surgery‑related factors while
late hydrocephalus is either due to tumor recurrence or
radiation‑induced changes.[48] In the ensuing discussion, PRH
refers only to “early” hydrocephalus.
The incidence of PRH differs significantly between children
and adults as noted earlier. Marx noted that the incidence of
hydrocephalus following PFT resection in adults is as low as
1.6%.[2] In children, the incidence of PRH varies between 10
and 40%.[19,22,24,25,32,49]
PRH increases the risks of immediate postoperative
complications like CSF leakage, pseudomeningocele, and
prolonged hospital stay.[35]
What are the Risk Factors for PRH?
Cully and colleagues analyzed 117 patients and found
the following factors to be associated with a higher
incidence of PRH: age  <3  years, midline tumor location,
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S345
subtotal resection, prolonged EVD requirement, cadaveric
dural grafts, pseudomeningocele formation, and CSF
infections.[25] Due‑tonnessen and Hleseth found that patients
with medulloblastoma and ependymoma had much higher
rates of postoperative shunt placement than astrocytomas.[36]
Kumar and colleagues in a study of 196 consecutive children
found age  <3  years, tumor histology of medulloblastoma/
ependymoma, and partial resections were associated with
the increased chances of postresection hydrocephalus.[9] A
recent study noted that the only modifiable risk factor for the
development of PRH was the presence of intraventricular
blood in postoperative imaging.[48] Intraventricular blood can
cause hydrocephalus either by the “snow globe effect”[50] or by
other factors like impaired absorption of CSF by inflammation
and fibrosis of the arachnoid granulations caused by blood
degradation products.[48]
Gopalakrishnan and colleagues noted the following risk
factors for PRH: the need for CSF diversion in the pediatric
population—children with symptomatology  <3  months
duration, severe hydrocephalus at presentation, tumor location
in the midline, tumor histology, viz. medulloblastoma and
ependymoma, use of intraoperative EVD, longer duration of
EVD, postoperative meningitis, and pseudomeningocele.[11]
Similar findings were also reported by Bognar et al.[24] who
showed that the presence of EVD and the duration of EVD
were associated with a significant increase in the incidence
of postresection CSF diversion. In another recent study,
Pitsika et al.[19] showed that patients who underwent EVD had
a higher rate of postoperative VPS. They also noted a negative
correlation between early EVD clamping and VPS indicating
that clamping encourages the re‑establishment of normal CSF
flow when the obstructive tumor is removed.
Is it Possible to Predict the Occurrence of PRH?
Riva‑Cambrin and colleagues used a large cohort of 331 patients
and developed the Canadian Preoperative Prediction Rule
for Hydrocephalus  (CPPRH) for the identification of at‑risk
patients for PRH using a weighted scoring system that gives
higher scores to the factors associated with a higher incidence
of PRH like age <2 years, presence of papilledema, moderate or
severe hydrocephalus, metastases, and preoperative diagnosis
of medulloblastoma/ependymoma.[23]
This CPPRH was subsequently validated by Foreman et al.[51]
who modified the CPPRH by replacing papilledema with the
radiological evidence of transependymal flow of CSF [Table 1].
A score of 5–10 is considered high risk and scores between 0
and 4 are considered low risk. These two scoring systems can
be used to guide the clinicians for the optimal management
of hydrocephalus preoperatively so that more aggressive
measures like CSF diversion (internal or external) can be
instituted in children with high risks. However, more recently,
an independent study by Pitsika et al.[19] failed to validate
the CPPRH. Pitsika et al.[19] in an analysis of 75 patients
retrospectively to validate the Modified Canadian Preoperative
Prediction to Rule for Hydrocephalus (mCPPRH)  showed
that if they had used the high‑risk category as defined by
mCPPRH, it would have resulted in 42% of more patients
undergoing unnecessary surgery. In addition to the above,
the CPPRH and mCPPRH do not take into consideration the
 Muthukumar: Hydrocephalus associated with posterior fossa tumors

extent of the resection of the tumor which may be a major patient positioning, and the expected extent of resection of
determinant for the persistence of symptomatic hydrocephalus the tumors, and for extraparenchymal tumors, the predictive
in the postoperative period.[48] Interestingly, in a recent study factors were preoperative hydrocephalus, tumor location, and
Srinivasan et al.[42] showed that the risk of preresection ETV perilesional edema.[29] They propounded that the patients with
failure was higher with a higher mCPPRH score which negates a score of 3 or more should undergo prophylactic EVD, for
the very purpose of identifying patients at high risk. those with a score of 0—there was no need for CSF drainage
and for those with scores of 1 and 2, the need for perioperative
In adults, a novel grading system for predicting the need EVD placement should be decided on a case‑by‑case basis.[29]
for postoperative CSF diversion following posterior fossa Marx et al.[27] noted that in adult patients with PFT, the need
tumor surgery was postulated by Won et al.[29] and is known for postresection CSF diversion like ETV or EVD was related
as the Frankfurt Grading System [Table 2]. They divided PFT to tumor location, leptomeningeal metastatic spread, and
into intraparenchymal and extraparenchymal tumors and complications due to tumor surgery.
proposed a four‑tier grading for intraparenchymal tumors
and a five‑tier grading system for extraparenchymal tumors; Molecular Subtype of PFT and the Risk of
for the intraparenchymal tumors, the predictive factors were Postoperative Hydrocephalus
preoperative hydrocephalus, periventricular CSF capping,
Schneider et al. [46] examined the molecular subtypes of
medulloblastoma in 130 pediatric patients and found that
Table  1: Modified Canadian preoperative prediction
those with the wingless (WNT) subgroup did not develop
rule for hydrocephalus[51]
hydrocephalus when compared to the other three groups, viz.
Predictor Score
Sonic Hedge Hog (SHH), group 3, group 4, with the highest
Age <2 years 3 incidence in group 4. The implication of this study is that it is
Presence of transependymal edema 1 now possible to preoperatively predict the molecular subtype of
Moderate/severe hydrocephalus 2 medulloblastoma both in children and adults by radiogenomics
Cerebral metastases 3 with reasonable accuracy as shown by the studies of Dasgupta
Preop estimated tumor diagnosis et al.[52] and Kleil et al.[53] Therefore, radiogenomics can be used
Medulloblastoma 1 preoperatively to identify at‑risk patients for the development
Ependymoma 1 of hydrocephalus.
Dorsal exophytic brainstem glioma 1
Total score 10 Pathophysiology of PRH
From Foreman et al.: J Neurosurg Pediatrics 2013; 12:220‑226[51]
The exact cause for the persistence of ventriculomegaly after the
Table 2: Frankfurt Grading System for the prediction resection of PFT is not known but may be multifactorial. In one
of postoperative hydrocephalus in adults with PFT[29] study, the rate of the reduction of ventricular volume after the
resection of PFT was evaluated and it was found that both in
Tumor category and predictive variables Points
the patients with or without the need for postoperative shunt,
Intraparenchymal tumors
the rate of reduction in the ventricular volume was the same
Hydrocephalus
and these authors concluded that in the patients with PFT, the
Yes 1 resection of the tumor converts obstructive hydrocephalus to
No 0 communicating hydrocephalus.[54] The idea that PRH in PFT is
Periventricular CSF capping communicating is certainly not new as more than four decades
Yes 1 ago, Cabanes and colleagues in a radioisotope study showed that
No 0 the CSF flow is abnormal in the basal cisterns and suggested that
Surgical position PRH may be communicating.[55] Bateman and Fiorentino, in an
Other than semi‑sitting position (park bench/prone 1 interesting study, calculated the ventricular volumes as well as
Semi‑sitting 0 the cross‑sectional areas of the venous sinuses both before and
Expected extent of resection after surgery and noted that preoperatively there was a 70%
Subtotal 1 decrease in the cross‑sectional area of the venous sinuses and
Total 0 the same were restored to normal 4 months after the surgery.[56]
Extraparenchymal tumors They showed that venous sinuses are compressed by the PFT and
the raised ICP leading to a venous outflow obstruction and the
Location
sinuses do not get restored to their normal cross‑sectional area
Petroclival 2
until several weeks after the surgery and this might be the reason
Midline 1
for PRH. This interim period during which the ventricles remain
Lateral 0
larger than normal despite total tumor removal and restoration
Perilesional edema of the CSF pathways is known as the adaptation period. Nishiyama
Yes 2 and colleagues showed that it takes several days for the CSF
No 0 bulk flow to reopen the peripheral subarachnoid spaces and to
Hydrocephalus restore CSF absorption at the arachnoid granulations[57] further
Yes 1 emphasizing the communicating nature of the hydrocephalus.
No 0 Cinalli and colleagues measured the ICP after ETV in patients
From Won et al.: J Neurosurg 2020: 132:296‑305[29] with PFT and those with shunt dysfunction.[18]

S346 Neurology India | Volume 69 | Supplement 2 | November-December 2021

 Muthukumar: Hydrocephalus associated with posterior fossa tumors
They showed that in the majority of the patients, there was an
“adaptation period” during which the ICP remained raised
and this increased ICP could be managed with 1–3 lumbar
punctures with ICP monitoring, and thus, permanent CSF
diversion could be avoided. They postulated that these lumbar
punctures increase the compliance of the spinal subarachnoid
space, thereby, increasing the pressure gradient across the
stoma. If the same logic can be extended to the patients with
persistent ventriculomegaly following the re‑establishment
of the CSF pathway after PFT resection, the possibility of
lumbar punctures in carefully selected patients decreasing
the need for postresection shunting could be considered for
future studies.
Management of PRH
ETV and VPS continue to remain the mainstay in the
management of PRH.[33] Tamburrini and colleagues treated
30 patients who developed PRH with ETV with a success rate
of 90%.[33] Gopalakrishnan and colleagues treated 80 patients
with symptomatic hydrocephalus and PFT and found 30% with
PRH all of whom were treated by VPS.[11]
Hydrocephalus in Brainstem Gliomas
The literature on the management of hydrocephalus associated
with brainstem gliomas in children is controversial. Amano and
colleagues reported 18 patients with brainstem glioma of whom
16 developed hydrocephalus who were treated predominantly
by VPS, two with Torkilsden shunts, and three with
ETV.[58] They noticed that the patients treated for hydrocephalus
survived longer than those who did not undergo such treatment
and recommended early identification and management
of hydrocephalus in brainstem gliomas. [58] However, in
another large study, Rojeau et al.[59] studied 51 patients with
brainstem gliomas in whom hydrocephalus occurred in
22%. Hydrocephalus was treated by VPS and ETV. ETV was
associated with early failure. These authors concluded that
the treatment of hydrocephalus did not influence the ultimate
outcome of these patients. Interestingly, in both the studies, the
average time for the development of the hydrocephalus after
the tumor diagnosis was 5 months, and therefore, the patients
with brainstem gliomas should be kept under surveillance
for the early identification of hydrocephalus. Both studies
cautioned that ETV should be used with great care in this group
of patients as the tumor in the brainstem would have distorted
the brainstem and changed the anatomy of the prepontine and
interpeduncular cisterns making ETV riskier.[58,59]
Conclusions
PFT ‑associated hydrocephalus is more common both at
presentation and after tumor resection in children than in
adults. The current trend in the literature is toward the use
of early primary tumor resection, thus, avoiding the need
for preoperative CSF diversion. However, clinical judgment
should be used regarding the preoperative use of ETV or the
perioperative use of EVD depending upon the patient’s clinical
status, logistics, etc. In children, there is a 30% chance of PRH.
This warrants an aggressive surveillance protocol for the
identification of at‑risk patients. ETV with its low complication
rates is becoming increasingly popular for the management
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S347
of PRH. However, in children with aggressive tumors with
metastases at the time of presentation, it might be prudent to
consider the option of VPS in view of the early and high failure
rates of ETV in this subgroup.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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 Original Article

Access this article online

Quick Response Code:
Management of Complex
Hydrocephalus
Abhirama Chandra Gabbita, Subodh Raju

Website: Abstract: 
www.neurologyindia.com
Background: Management of complex/multiloculated/septated hydrocephalus is challenging. Neuroendoscopy
DOI: has been well‑established when compared to multiple shunt placements in management of multiloculated
10.4103/0028-3886.332284 hydrocephalus (MH). The main aim of neuroendoscopy is to convert multiple locules into a single locule and
drain it by either third ventriculostomy or ventriculoperitoneal shunt.
Objective: The objective is to reduce the number of surgical procedures and improve the quality of life.
Neuroendoscopy avoids multiple shunt placement and need for revision of shunt.
Methods: Literature review regarding natural history, pathogenesis, classification and management of
complex/uni/multiloculated hydrocephalus was extensively done and our minimal experience with these cases
has been taken into consideration.
Conclusion: Neuroendoscopy when combined with frameless neuronavigation is reliable, accurate, and
extremely useful in maintaining orientation and localizing the appropriate fenestration site in MH where
anatomical landmarks are grossly distorted.
Key Words:
Complex hydrocephalus, loculated, neuroendoscopy, septated, ventriculitis

Key Message:
Complex hydrocephalus is a challenging neurosurgical problem. Extensive agreement has been reached
considering neuroendoscopic procedures as the reference standard for the treatment of complex hydrocephalus.

C omplex hydrocephalus (CH) is due

to the combination of obstructive and
communicating hydrocephalus—obstruction
and defective absorption of CSF. Loculated
hydrocephalus refers to the presence of an isolated
CSF compartment or compartments within the
ventricular system that may progressively
enlarge, despite a functioning shunt system.[1]
effective procedure. Endoscopy has an advantage
of minimal invasiveness and effectiveness of
microsurgery.[6]
Incidence of CH is about 2.3–14% across various
studies. [7‑9] The incidence is higher for post
infectious hydrocephalus (31%) than congenital
hydrocephalus (12–14%).

Definitive treatment is surgical, yet the ideal Natural history and pathogenesis
approach remains debated. Traditional treatment While its pathogenesis is not fully understood,
consisted of shunting, requiring placement of CH is linked to neonatal bacterial meningitis,
Department of multiple shunt systems and multiple revisions,[2,3] germinal matrix hemorrhage, or ventriculitis
Neurosurgery, Institute stereotactic aspiration of cysts and communication from shunt infection. Predisposing factors
of Neurosciences, AIG of the compartments; microsurgery with lysis of include low birth weight, premature birth,
Hospitals, Mindspace intraventricular cysts had been advocated in perinatal complications, and congenital CNS
Road, Gachibowli, historical era.[4,5] malformations.[10]
Hyderabad, Telangana,
India Endoscopic cyst fenestration either alone or The excess drainage of CSF via a ventricular
in combination with endoscopically assisted shunt system can cause ultrastructural changes in
Address for ventriculoperitoneal shunt is being favored in the the CSF pathways and lead to the partitioning of
correspondence:
treatment of multiloculated hydrocephalus (MH) compartments. The obstruction of the foramen of
Dr. Subodh Raju,
Department of because it is a simple, minimally invasive, and Monro in isolated unilateral hydrocephalus and
Neurosurgery, 1st Floor
Cluster Q, AIG Hospitals, This is an open access journal, and articles are distributed under the terms How to cite this article: Gabbita AC, Raju S.
Mindspace Road, of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 Management of Complex Hydrocephalus. Neurol
Gachibowli, Hyderabad, License, which allows others to remix, tweak, and build upon the work India 2021;69:S350-6.
Telangana, India. non‑commercially, as long as appropriate credit is given and the new
creations are licensed under the identical terms. Submitted: 12‑Aug‑2021 Revised: 16-Sep-21
E‑mail: subodh61raju@ Accepted: 18‑Oct‑2021 Published: 11-Dec-2021
gmail.com For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com

S350 © 2021 Neurology India, Neurological Society of India | Published by Wolters Kluwer - Medknow
 Gabbita and Raju: Management of complex hydrocephalus

aqueductal obstruction in isolated fourth ventricle after shunt

placement occurs in a previously communicating ventricular
system, and in both cases a reduction in the size of all ventricles
is initially seen after shunting. Isolation then gradually
develops, and further enlargement of isolated compartment
is observed. Various types of isolation may then develop,
depending upon the site of occlusion.[11,12]

The inflammation and destruction of the ependyma

allows glia to project into the lumen, spanning and
obstructing crucial areas (e.g., the intraventricular foramina,
aqueduct, foramen of luscka, and magendie). It is thought
that intraventricular septations probably represent
the organization of exudates and debris produced by
ventriculitis, regardless of whether it is of a chemical or of an
infectious nature. Microscopically, the septations are made
of fibroglial elements with polymorphonuclear cells. The
inflammatory response of the ependymal surface might lead Figure 1: Isolated occipital horn of left lateral ventricle
to the genesis of the fibroglial septas.[13] The septation not
only changes the ventricular anatomy, but also deranges the
normal flow of CSF; thus the production and accumulation
of CSF within a loculated cavity can lead to progressive
dilatation and mass effect.

Classification
CH can be temporary or permanent based on whether the
defective absorption and or defective permeation of CSF
through subarachnoid space is transient or persistent.[14]

CH is further sub‑classified as either uniloculated or

multiloculated. Uniloculated hydrocephalus is either
supratentorial (isolated lateral ventricle) [Figure 1] or
infratentorial (isolated fourth ventricle) [Figure 2]. Uniloculated
hydrocephalus is generally congenital with unaffected CSF
pathways, whereas MH [Figure 3] is generally postinfectious
or postinflammatory with obliterated subarachnoid spaces.[15]
Figure 2: Trapped 4th ventricle
Clinical features
Children present with raised intracranial pressure leading
to macrocephaly in infants and headache in older children.
Other symptoms include seizures, gait ataxia, and hemiparesis,
intractable seizures.[10] Developmental delay is reported to
be more common in multiloculated than uniloculated cases.
Trapped fourth ventricle patients can also present with
various neurological manifestation starting from simple ataxia,
vomiting to quadrparesis, and so on.

Management
Diagnosis
The diagnosis of CH is usually evaluated through computed
tomography (CT scan) or a magnetic resonance image (MRI).
But they cannot accurately disclose communication between
cavities. In previous years, pneumoventriculography and
contrast ventriculography were performed, as they are invasive
techniques; but they are currently considered only in selective
cases.

Constructive interference in steady‑state (CISS), and

three‑dimensional Fourier transformation (FIESTA) sequences
allow for the visualization of intracystic and intraventricular
septa that cannot be visualized by using T2‑weighted Figure 3: Six months child, post meningitis &amp; post ventriculitis, post VP shunt
imaging.[16] with progressive increase in head size –multiloculated hydrocephalus

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 Gabbita and Raju: Management of complex hydrocephalus

CISS/FIESTA, DRIVE, cine phase sequences allow the

membranes of individual compartments to be better
visualized, and provides a clearer distinction of uniloculated
hydrocephalus from the multiloculated variant.[17]

As CH is an evolutive process [Figures 4 and 5a, b], patients

need to be followed up periodically with imaging and clinical
condition. The use of CT scanning for follow‑up purpose in
neonatal meningitis patients will facilitate early diagnosis
of compartmentalization of ventricles, document evolution
and progression of hydrocephalus, and help in the earlier
a b
diagnosis of shunt malfunction. In newborn, follow‑up with
ultrasonography can be employed to avoid radiation. Figure 4: (a) Trapped temporal horn, (b) progression of dilatation, underwent
biventriculo-peritoneal shunt
Treatment
The definitive treatment of CH is surgical. The goal of treatment
in this complex disease is to restore communication between
isolated intraventricular compartments [Figure 6] in order
to create a unique ventricular cavity and to implant a single
shunt with only one intraventricular catheter, reducing shunt
revision rate, avoiding implanting multiple shunts if possible,
and decreasing operative morbidity.[10]
a
Traditional treatment consisted of using shunts with
multiperforated ventricular catheters. But, shunting alone is
always unsuccessful. Scaring and collapse of the cyst around
the catheter tip frequently lead to shunt malfunction. Multiple
or complex shunts are often placed in an attempt to balance
CSF production and absorption between the cyst and the
ventricular system. However, embedded ventricular catheters,
b
which cannot be removed without the risk of intraventricular
hemorrhage, may serve as a nidus for infection and contribute Figure 5: (a and b) Serial images done at an interval of 6 months in a case of post
to cyst infection. Such treatment had an increasing rate ventriculitis hydrocephalus, displaying the dynamism of this disease
of mechanical shunt failure and infection leading to high
morbidity and mortality. [18] Different trapped/septated
ventricles may have different nature of CSF and some may still
be having infection. A contrast imaging and CSF analysis from
each may be helpful to plan a procedure [Figure 7].

Stereotactic aspiration is considered to be a blind procedure.[19]

Importantly, simple aspiration leads to high recurrence rate
(up to 80%), as the stereotactic procedure fails to devascularize
the cyst or to create a large window in the cyst wall.

The first septal fenestration through craniotomy was

published by Rhoton et al.[20] in 1972. They reported an infant
with progressive hydrocephalus due to meningitis with
multiple obstructing membranes within lateral ventricles. The
hydrocephalus was tackled with a shunt after the excision of
the membranes through right parietal craniotomy. Advocates
for using the microsurgical procedure say that hemostasis can Figure 6: Surgery: Left frontal burr hole, Intraventricular multiple septostomies
be well achieved as the intraventricular septations are dissected
under direct vision. In 1995, Lewis et al.[21] published the first large series of patients
who underwent endoscopic treatment of MH and achieved the
Nevertheless, there are drawbacks for the microsurgical reduction of the shunt revision annual rate from 3.04 to 0.25.
procedure. The transcallosal surgery is technically After this publication, neuroendoscopy became popular in the
demanding with unintended damage to the pericallosal treatment of CH.
arteries, fornix. The transcortical approach has risk of
seizures and subdural collection, as the cortical mantle is In 2003, Nowosławska et al.[22] compared two groups of patients
often thinned out from hydrocephalus and also the loss suffering from MH, one treated with endoscopic procedures
of CSF during cyst decompression leads to collapse of the and the other with conventional shunt. They not only found
ventricular wall. that endoscopy reduced the shunt revision rate, but also

S352 Neurology India | Volume 69 | Supplement 2 | November-December 2021

 Gabbita and Raju: Management of complex hydrocephalus

children treated with this procedure were in much better
clinical condition than the other group.
In 2008, El‑Ghandour et al.[23] advocated that fenestration has to
be atleast 1 cm or more in diameter made with either forceps,
scissors, or Fogarty balloon and to devascularize the septa to
prevent regrowth because of high incidence of closure of small
openings caused by the low‑pressure differential across cyst
walls and the inflammatory origin of the disease.
However, we have to keep in mind that intraoperative changes
like brain shift and cyst drainage invalidate preoperative
planning. The two factors that help to minimize this brain shift
effect during neuronavigation aided ventricular endoscopy are
gradual step‑by‑step opening of the isolated compartments to
minimize CSF loss and continuous irrigation throughout the
procedure. In some cases where the anatomy is so altered that
imaging for navigation is confusing, sonography guidance is
the best modality to achieve real‑time image navigation.[27]

The preference of endoscopic approach depends on the septa Technique of ETV

location. In uniloculated hydrocephalus, cystoventriculostomy
offers best chance of treatment for these patients [Figure 8].
Isolated lateral ventricles can be treated by Septum
pellucidotomy/foraminoplasty [Figure 9].
Isolated fourth ventricle can be treated by endoscopic
transventricular transforaminal aqueductoplasty and or
aqueductal stenting.[24] The tip of catheter is placed in the fourth
ventricle and is perforated proximally so as to communicate
the fourth and lateral ventricles. It’s then connected to a shunt
system [Figure 10].
In these complex hydrocephalic endoscopic procedures,
neuronavigation system is often used to guide the tip
of the endoscope. Such a system, especially frameless
navigation is useful in the preoperative planning of
burr hole placement and to define the trajectory to the
target[25,26] [Figure 11a‑d].
The burr hole is placed selectively on the nondominant side, just
infront of the coronal suture and 3 cm from midline. Once third
ventricle is entered, anatomical landmarks are identified; stoma
is made between the mammillary bodies and infundibular
recess. Care is taken to stay in the midline and not to wander
behind the basilar artery complex. The final stoma should be
a minimum of 4 mm in diameter.[28]
Technique of septum pellucidotomy
The burr hole is better made on the same side as the larger of
the two lateral ventricles. The burr hole is placed just anterior to
the coronal suture and about 5 cm away from the midline. This
allows a more lateral approach to septum and a less likelihood
of damaging the structures in the floor of contralateral ventricle.
The optimal place to make the communication is approximately
1 cm anterior and 1 cm above the foramen of Monro. The
septum is opened between the anterior and posterior septal
veins, that is, the most avascular and thinnest area of the septum
pellucidum. An alternative trajectory to the septum pellucidum

Figure 7: Enlarged isolated left sided ventricles managed with ventriculo peritoneal shunt, Enlarged isolated right ventricle with active infection managed with ventriculo
subgaleal shunt

a b
Figure 8: (a) MRI images showing Trapped 3rd ventricle, (b) endoscopic septostomy

Neurology India | Volume 69 | Supplement 2 | November-December 2021 S353

 Gabbita and Raju: Management of complex hydrocephalus
b
c Technique of aqueductoplasty
Figure 9: 11 yr old boy a case of hydrocephalus due to aqueductal stenosis,
already shunted, (a) Trapped Rt lateral ventricle due to obstruction at Foramen of
Monroe, (b) Closed foramen due to membrane and choroid plexus. Foraminoplasty
and 3rd ventriculostomy done, (c) Post op CT showing well decompressed ventricles
(if there is a pre‑existing shunt in the ipsilateral ventricle) is via
a posterior parietal burr hole (Keyne’s point).[29]
Technique for multicompartmental hydrocephalus
Burr hole placement in the context of multicompartmental
hydrocephalus is variable. Patient anatomy and the presence of
pre‑existing ventricular catheters dictates positioning.[30] Several
important principles that guide the surgical approach are:
1. The burr hole is made in that position where the cortical
passage is as short as possible, so the endoscope will
enter the largest cavity, and this trajectory will guide the
endoscope to the membrane that separates the two cavities
that needs to be joined.
2. If there is a pre‑existing ventricular catheter that is not
draining an isolated part of the ventricle, then it will be
effective to utilize the pre‑existing tract to the ventricle,
even if the cavity that needs to be entered is smaller.
3. If there are multiple loculations, the trajectory should
always aim to communicate as many cavities as possible.
4. If the patient never had a shunt placement, attempts
should be made to break down all the membranes before
performing extracranial CSF diversion.
5. The more the number of fenestrations that are made,
the more are the chances that cavities will continue in
permanent communication.
6. The membrane should be opened with any of the available
sharp tools such that the diameter is atleast 4 mm.
Technique of cyst fenestration
In cases of arachnoid cysts, the fenestration is to be made
between the cyst and the basal cisterns. No shunt material
S354 Neurology India | Volume 69 | Supplement 2 | November-December 2021
a b
c d
Figure 10: (a) Trapped 4 ventricle with hydrcephalus, (b) transaqueductal catheter
th
placement after aqueductoplasty, (c) post op images showing well decompressed
4th ventricle, (d) X-ray skull showing the catheter in the 4th ventricle, traversing the
the lateral ventricle and connected to a shunt
is to be left in the hole to maintain the communication. The
exceptions to this rule are suprasellar cysts. Every attempt is
to be made to perform ventriculocystocisternostomy, but when
communication between the cyst and the cisterns is considered
too dangerous, ventriculocystostomy is very much acceptable.[31]
When the ventricles are enlarged, the approach to the fourth
ventricle should be attempted through the third ventricle via
a burr hole placed approximately 8 cm behind the nasion
and 3 cm from the midline. Once the aqueduct is identified,
it is dilated using a combination of hydrodissection and a
balloon catheter. A standard‑sized ventricular catheter can
be customized and left within the aqueduct. When the lateral
ventricles are small, the aqueduct is approached by a steerable
flexible endoscope from below through a limited midline
suboccipital craniectomy.[32]
Endoscopic armamentarium
Rigid endoscopes are usually preferred because they have
greater light intensity and superior optics, which allow better
visualization. The limited piloting of rigid endoscopes is
usually offset by careful selection of the burr hole placement
site and by widening the outer edge of the burr hole, which
provides greater liberty.
Flexible endoscope has been preferred by some neurosurgeons
due to its flexibility and steerability, which provides increased
maneuverability. However, it requires a significant amount
of expertise and its main role in MH is navigating through
ventricular system and performing aqueductoplasty in cases
with isolated fourth ventricle and selecting different trajectories
and alternative stoma when standard third ventriculostomy
becomes difficult.[33‑35]
Different methods of fenestrating intraventricular cysts have been
reported such as argon laser, Nd: YAG (neodymium: yttrium
aluminum garnet), thulium laser, saline torch, and bipolar
cautery.[36,37] Ventricular catheters embedded in scar tissue or
adherent to the choroid plexus, which previously could not be
withdrawn safely without risking intraventricular hemorrhage,
can be removed under direct vision with endoscopic assistance
and laser. The YAG/thulium laser can be used to coagulate the
 Gabbita and Raju: Management of complex hydrocephalus

choroid plexus and to cut along the interface of the scar, and
the silicone tubing to dislodge the catheter.
Complications
Major complications of cyst fenestration and septostomy
include ventricular hemorrhage, ventriculitis, injury to adjacent
neural tissue, and CSF leakage. Hemorrhage and ventriculitis
may lead to further loculations.
The risk of injury to adjacent neural tissue can be minimized
by careful planning of the surgical approach and by having
a knowledge of the neural structures beyond the point of
fenestration. Consequently, orientation is critical and therefore
the intraoperative use of ultrasound and stereotaxis in
conjunction with endoscopy is so helpful.
Discussion
The outcome in this complex disease depends on the surgical
procedure as well as the sub type of CH. The outcome is
assessed by the incidence of improvement of hydrocephalus
in postoperative imaging, avoiding or eliminating the need for
shunting, simplifying complex shunt systems, and reducing
shunt revision rate. Uniloculated hydrocephalus is simpler to
treat endoscopically than MH and consequently, it carries a
better prognosis.
In the senior author’s (SR) experience 64 cases of CH had been
treated by endoscopic procedure (rigid and flexible); mean age
at presentation was 16 months. Endoscopic cyst fenestration
with revision of VP shunt was done in 33 patients (51.5%),
endoscopic cyst fenestration with choroid plexus coagulation
was done in 19 patients (29.6%), and 12 patients (18.8%)
underwent endoscopic aqueductoplasty and stenting. The
shunt revision rate was significantly better post endoscopic
procedure, 15 patients (22.7%) required re‑exploration/
revision of shunt. Forty‑nine patients (81.3%) required no
further procedure.
It has been reported across major series that 84% of patients
undergoing endoscopic cyst fenestration for unilateral
hydrocephalus have either remained shunt free or not required
additional shunt placement.
Endoscopic procedures reduced the shunt revision rate from
2.9 per year before fenestration to 0.2 per year after fenestration.
After the endoscopic procedure, Teo et al.  reported a shunt
rate of 72%; El‑Ghandour, a shunt rate of 88%; Spennato et al.,
a 73% rate; Zuccaro and Ramos, 98%; Schulz et al., 100%; and
Lewis et al., 79% [Table 1].
Conclusions

After an extensive review of all the literature about this complex

a b
c d
Figure 11: (a) Neuro navigation guided planning to include maximum cavities,
(b,c,d) the endoscopic septostomies are done in such a way to target the preexisting
functioning shunt and draw it into the multiple cavities through these septostomies
disease and taking into account the experience we gathered
during all these years in the treatment of these patients, we
can postulate the following conclusions:
1. MH is a severe disease in which no single treatment has
clearly been proven to be superior.
2. The goal of treatment is to restore communication between
isolated intraventricular compartments in order to create
the possibility of implantation of a simple shunt with only
one intraventricular catheter.
3. Neuronavigation and or intraoperative ultrasound imaging
should be performed in all cases in which the ideal
trajectory needs to be established.
4. Extensive agreement has been reached considering
neuroendoscopic procedures as the reference standard for
the treatment of CH.
5. In cases of hydrocephalus with scarce cortical mantle,
bilateral choroid plexectomy should be considered after
the fenestration of intraventricular septas in order to avoid
a shunt.

Table 1: Results and outcomes in treatment of complex hydrocephalus across large international series
Investigator Patients (n) Follow‑up in Revision of endoscopic procedure (n) Shunt infection Shunts present at last follow‑up
months (n, %)
El‑Ghandour, 24 30 One in eight 0, 0% 21 patients had one shunt (88%),
2008[23] three had none
Schulz et al., 16 19 Four in one patient three in three patients 4 (13.8%) Six patients had two shunts (all
2010[37] two in two patients 100%) 10 had one shunt
Zuccaro et al., 47 NR One in 30 patients two in eight patients 1 (2.8%) 21 patients had one shunt (88%)
2011[10] three had none
Teo et al., 114 65 One in one 1 (0.69%) 82 patients had one shunt (72%) 32
2013[30] had none (22%)
Tamburrini et al., 68 50 One in 21 patients two in five patients 11 (16%) Four patients had one shunt (all
2018[36] three in two patients four in one patient 90%), 17 had two, seven had none
1
Results and outcomes in treatment of CH across large international series

Neurology India | Volume 69 | Supplement 2 | November-December 2021 S355

 Gabbita and Raju: Management of complex hydrocephalus
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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 Original Article

Access this article online

Quick Response Code:
Evaluation and Management of
Patients with Hydrocephalus in
Craniosynostosis
Jaime Grant, Jagajeevan Jagadeesan, Pasquale Gallo, Desiderio Rodrigues
Website:
www.neurologyindia.com

DOI: Abstract:
10.4103/0028-3886.332272
Background: Hydrocephalus in presence of craniosynostosis, though relatively rare, occurs in 4%–10%
cases, with an increased incidence in syndromic craniosynostosis. The optimum management in these
patients is unknown.
Materials and Methods: A search was performed on the departmental craniofacial database to identify all
patients with craniosynostosis and hydrocephalus from January 2000 to December 2020. Diagnosis was
confirmed by a meticulous review of the notes and previous imaging. These patients were grouped into two
groups based on the primary treatment they received: either a cerebrospinal fluid (CSF) diversion procedure
or a calvarial remodeling procedure. By analyzing the outcomes for each group, we endeavor to rationalize
and outline our management strategy for this complex cohort of patients.
Results: Sixty‑four of 989 patients were confirmed to have hydrocephalus. Of these, 55 patients underwent
calvarial expansion while nine had CSF diversion as a primary procedure. Our study demonstrates that the
complication rate is lower in the primary calvarial expansion group. Furthermore, the need for a CSF diversion
procedure was avoided in a significant number of these patients as a direct result.
Conclusion: In the vast majority of patients with craniosynostosis and hydrocephalus, calvarial expansion
surgery should be the preferred primary management option.
Key Words:
Calvarial expansion, craniosynostosis, CSF diversion, hydrocephalus, syndromic

Key Messages:
Hydrocephalus secondary to craniosynostosis requires addressing the underlying problem.

H ydrocephalus is defined as active distension

of the ventricular system of the brain
resulting from the inadequate passage of
cerebrospinal fluid  (CSF) from its point of
production within the cerebral ventricles
to its point of absorption into the systemic
circulation.[1] Hydrocephalus occurring in the
presence of craniosynostosis is relatively rare.[2‑4]
It occurs in approximately 4% to 10% of patients
Department of with craniosynostosis, the majority of which
Craniofacial Surgery, are syndromic patients. [4‑8] The incidence is
Birmingham Women’s increased in syndromic cases such as those with
and Children’s Hospital Apert or Pfeiffer syndrome, where it is reported
NHS Foundation Trust, to be as much as 40%–50%.[9] In 2005, Collmann
United Kingdom et al.[9] postulated the following three statements,
which hold true to date. (1) Enlarged ventricles
Address for
may represent “true” hydrocephalus requiring
correspondence:
Mr. Desiderio Rodrigues,
intervention or a passive ventriculomegaly
Department of Craniofacial process.  (2) Hydrocephalus is seen mainly
Surgery, Birmingham
Children’s Hospital, This is an open access journal, and articles are distributed under the terms
Steelhouse Lane, of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0
Birmingham, B4 6NH, License, which allows others to remix, tweak, and build upon the work
United Kingdom. non‑commercially, as long as appropriate credit is given and the new
creations are licensed under the identical terms.
E‑mail: desiderio.
rodrigues@nhs.net For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com
in the complex forms of craniosynostosis.  (3)
The combination of the two conditions poses
problems with diagnosis as both cause raised
intracranial pressure  (ICP) but via opposing
mechanisms: expansion  (hydrocephalus) and
constriction (craniosynostosis).
The exact etiology of hydrocephalus in
craniosynostosis is not known, but it is believed
to be unique in terms of its pathogenesis, clinical
significance and presentation, radiological
appearance, and treatment.[8] The possible etiologic
factors for hydrocephalus in craniosynostosis
could either be as a result of either CSF outflow
obstruction[10,11] or impaired CSF absorption due
to venous hypertension.[12] Both of these are
directly or indirectly related to bony pathology.
How to cite this article: Grant J, Jagadeesan J,
Gallo P, Rodrigues D. Evaluation and Management
of Patients with Hydrocephalus in Craniosynostosis.
Neurol India 2021;69:S357-61.
Submitted: 01‑Jul‑2021   Revised: 20‑Aug‑2021
Accepted: 08‑Sep‑2021   Published: 11-Dec-2021

© 2021 Neurology India, Neurological Society of India | Published by Wolters Kluwer - Medknow S357
 Grant, et al.: Management of hydrocephalus in craniosynostosis

Hydrocephalus in craniosynostosis was first reported in
the literature in 1919.[3] Many case series and case reports
have been published since then discussing the incidence of
hydrocephalus in craniosynostosis. However, given that
these studies are poorly powered, there is no consensus
with regard to optimal management. This is in part due
to the complex pathophysiology of hydrocephalus in this
group of patients resulting in opposite forces exerted on the
intracranial volume by the dynamics of both these conditions;
with hydrocephalus acting as pressure from within and
craniosynostosis acting as a restriction from outside. The
pathophysiology of raised intracranial pressure (rICP) due to
hydrocephalus is expansile from within the cranial vault and
acts in opposition (but compounding in terms of increasing the
ICP) to the pathophysiology of rICP due to craniosynostosis
which is anatomically restrictive.[7,9,10] Thus, it is imperative
to have an accurate diagnosis to avoid long‑term recurring
complications associated with the management of both these
conditions when they exist in unison.
When considering the optimal management of hydrocephalus
in the presence of craniosynostosis, decisions are generally
made based on the clinical and radiological findings and the
previous experience of the team treating the patient. Due
to the restrictive nature of craniosynostosis, the parameters
indicative of hydrocephalus (accelerated head circumference,
bulging fontanelle, and radiological features) are less reliable
or absent.[13]
Group  A: those treated with CSF diversion as a primary
procedure
Group B: those treated with calvarial expansion as a primary
procedure
Outcome measures
Primary outcome measures were based on the success of the
procedure, that is to say, the initial reason for undertaking
the procedure was resolved by that procedure. These were
structured as follows:
1. Successful procedure: no requirement for further procedure
2. Unsuccessful procedure: further procedure required due
to failure of the first procedure
Success was defined as resolution of raised ICP on clinical and
ophthalmological assessment.
Secondary outcome measures
To elucidate any factors that were predictive of failure or
success of a particular procedure for a particular patient,
the groups were analyzed in terms of demographics and
complications. In addition, complications were analyzed
separately to delineate any gross morbidity associated with
any particular management.
Results

In units routinely treating a large volume of syndromic Demographics

craniosynostosis cases, patients are regularly monitored
for any clinical features of rICP, with additional focus
on ophthalmology findings, including visual evoked
potentials (VEPs) where indicated. If there is any suggestion
of rICP on routine review, further investigation in the form
of radiology and sleep studies are carried out to differentiate
between hydrocephalus and craniocerebral disproportion or
other causes such as airway insufficiency. If there is significant,
rapid, and progressive ventriculomegaly, this may necessitate
an urgent CSF diversion procedure.
There remains ongoing debate when dealing with children
with craniosynostosis and concomitant hydrocephalus as to
what should be offered in the first instance: a CSF diversion
procedure or a calvarial remodeling procedure with close
observation and offering CSF diversion only if necessary.
This paper outlines our experience in the management of this
complex group of patients and our rationale for the strategy
adopted in our unit.
A total of 989  patients with a diagnosis of craniosynostosis
were treated during the study period. Sixty‑four out of
989 (6.5%) had hydrocephalus based on the agreed definition.
More patients were male  (male:  female  =  3.6:1). Moreover,
57/64  (89%) had a documented syndrome or multisuture
synostosis (with multisuture synostosis being either secondary
synostosis or likely (as yet) undefined syndrome, [Figure 1]
while the remaining seven were deemed to be nonsyndromic
patients due to single suture involvement. Of the nonsyndromic
patients presenting with hydrocephalus, the most common
suture involved was sagittal in five  (the other two being 1
bicoronal and 1 lambdoid suture synostosis). There were no
cases of isolated metopic suture synostosis presenting with
hydrocephalus.

Methods

A retrospective review of all craniosynostosis patients treated

in the craniofacial unit at the Birmingham Children’s Hospital
over a 20‑year period from 2000 to 2020 was performed. All
patients with confirmed hydrocephalus based on the study
definition were considered for inclusion.

Study groups
Patients were divided based on the nature of the primary
treatment they received: Figure 1: Subanalysis of syndromes and hydrocephalus

S358 Neurology India | Volume 69 | Supplement 2 | November-December 2021

 Grant, et al.: Management of hydrocephalus in craniosynostosis

Primary outcome measures procedure failed to resolve the rICP. Of these, one had a VP
Study groups shunt for a failed ETV and five had a calvarial expansion
The 64 patients identified with hydrocephalus were divided procedure [Figure 2].
into two groups based on the primary treatment they received.
Group B: Calvarial expansion as a primary procedure
Group A: CSF diversion (n = 9) Of these, 69%  (38/55) had resolution of the rICP while
31% (17/55) needed a secondary procedure to resolve their rICP.
Group B: Calvarial expansion (n = 55) This included 14 patients needing a CSF diversion (25.5%) of
which 11 had a ventriculoperitoneal shunt and three had ETV
Group A: CSF diversion as primary procedure [Figure 3].
Of these patients, eight had VP shunts and one had an
endoscopic third ventriculostomy (ETV) as primary procedure. Secondary outcome measures
Complications
Furthermore, 33% (3/9) had resolution of rICP while 66% (6/9) Twenty patients of the total 64 had complications significant
enough to require a return to theatre: 56%  (5/9) patients in
required a secondary procedure as the initial CSF diversion
group  A and 28%  (15/55) in group  B. The complications in
group A were all related to the CSF diversion procedure. In
Group  B, 9% of complications were related to the calvarial
expansion procedure while 18% were related to the secondary
CSF diversion procedure performed following the calvarial
expansion. In total, 65% (15/23) of patients who needed a CSF
diversion (VP shunt/ETV) had a complication needing further
surgical intervention [Figure 4].
a b c
Discussion

Management of hydrocephalus forms a major part of the

d e
Figure 2: CSF diversion as primary procedure in a child with Crouzon
syndrome. (a) Preoperative 3D CT Head of a child with Crouzon syndrome and
craniosynostosis. (b) MRI scan (T2W axial) showing acute ventricular dilatation with
periventricular edema. (c) MRI scan (T2W sagittal) showing small posterior fossa,
Chiari malformation, and hydrocephalus. (d) Postoperative 3D CT Head showing
calvarial remodeling after initial insertion of a ventriculoperitoneal shunt with a
programmable valve. (e) Postoperative CT Head (axial) showing the ventricles well
decompressed by downgrading the setting in the valve during surgery
workload of a Pediatric Neurosurgeon, but when dealing
with hydrocephalus in the presence of craniosynostosis, the
management is ill‑defined and varies greatly among various
units. This is in part due to the rarity of these conditions
coexisting and also due to the controversy with regard to the
etiology of hydrocephalus in patients with craniosynostosis.
There are two theories postulated:
1. Restrictive nature of craniosynostosis causing outflow
obstruction leading to hydrocephalus
Rieping theory  (1919) [14]: First described by Rieping
and later endorsed by others. In this theory, he
postulated that because of the constricted posterior
fossa in these patients, there is mechanical CSF outflow

a b c d

e f g h
Figure 3: Calvarial expansion as a primary procedure in a child with Crouzon syndrome. (a) 3D CT Head sagittal view showing craniosynostosis. (b) 3D CT Head occipital
view showing multisuture synostosis. (c) MRI Head (T2W sagittal) showing hydrocephalus due to outflow compromise. (d) MRI Head (T2W axial) showing dilation of frontal
horns with CSF effacement in occipital horns and pericerebral spaces. (e and f) Postoperative 3D CT Head (sagittal and occipital views) after calvarial expansion surgery.
(g and h) Postoperative MRI scans (sagittal and axial views) showing improved outflow and normal-looking lateral ventricles

Neurology India | Volume 69 | Supplement 2 | November-December 2021 S359

 Grant, et al.: Management of hydrocephalus in craniosynostosis

Figure 4: Flowchart detailing outcomes of patients with hydrocephalus and craniosynostosis

obstruction at the craniovertebral junction, resulting in

hydrocephalus.
2. Hydrocephalus existing due to venous pathology
Hoffman and Hendrick theory  (1979)[15]: Popularized
by Hoffman and Hendrick but described previously by
Günther (1939)[16] and Gross (1957),[17] this theory postulates
that the hydrocephalus is a result of impairment in CSF
absorption resulting from venous outflow obstruction
secondary to skull base anomalies in craniosynostosis,
especially around the jugular foramen.[12]

A literature search  (via PubMed) for a comparative study

of calvarial vault remodeling versus CSF diversion for
hydrocephalus in the presence of craniosynostosis yields
no direct comparative studies. Therefore, in deciding which
procedure to perform in the first instance, we must consider
the case in terms of symptoms and signs of rICP, radiological,
and fundoscopic findings (+/− VEPs).

Certainly, rapid progressive hydrocephalus necessitates

urgent management, which cannot be achieved in a timeous
fashion by calvarial remodeling and therefore may require
urgent CSF diversion. However, lifelong morbidity associated Figure 5: Algorithm: Case-based management of hydrocephalus in
with a shunt placement to treat childhood hydrocephalus is craniosynostosis
substantial.[18] This is also evident in the case series presented in
this study (65% of all patients with a shunt had a shunt‑related
While doing ETV in these patients, one needs to consider using
complication). Furthermore, there were a high number
a pediscope rather than a standard scope to minimize the
of patients who had a successful outcome from calvarial
backtracking of CSF. Furthermore, the prepontine area between
expansion alone. Therefore, we would recommend that in
the presence of craniosynostosis and hydrocephalus, it is the clivus and the basilar artery should be carefully assessed
worthwhile to perform a vault expansion procedure in the first and measured on preoperative MRI as the supratentorial
instance with close follow‑up for nonresolution or worsening crowding in these patients can compromise the space available
signs of rICP [see Figure 5]. to safely perform the stoma.

In addition to this, although ETV does not carry a high success
rate as a primary procedure for hydrocephalus in the presence
of craniosynostosis, it is our experience that ETV carries a
higher success rate after calvarial expansion surgery (especially
of the posterior fossa).[19]
We acknowledge that in spite of calvarial remodeling surgery,
some of these patients, especially those that are syndromic,
may go on to develop active hydrocephalus that may require
intervention. In addition, the patients who do require
CSF diversion procedures may go on to develop further

S360 Neurology India | Volume 69 | Supplement 2 | November-December 2021

 Grant, et al.: Management of hydrocephalus in craniosynostosis
shunt‑related complications  (e.g.  slit ventricular syndrome,
progression of Chiari, Syrinx formation, and recurrence of
raised intracranial pressure despite the CSF diversion). Thus,
it is paramount that this patient cohort is closely monitored
by clinical and ophthalmological examination and further
radiological studies undertaken at the appropriate time.
Conclusions
Hydrocephalus in craniosynostosis is a different entity from
nonsynostotic hydrocephalus. Primary treatment should be to
address the craniosynostosis with calvarial expansion surgery,
thereby resolving or arresting the hydrocephalus. However,
ongoing monitoring should be continued to evaluate the need
for further calvarial surgery or a CSF diversion procedure
should it be required. This pathway may avoid the need for any
CSF diversion procedure and its potential side effects and risks.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References
1. Rekate  HL. The definition and classification of hydrocephalus:
A  personal recommendation to stimulate debate. Cerebrospinal
Fluid Res 2008;5:2.
2. David DJ, Poswillo D, Simpson D. The Craniosynostoses: Causes,
Natural History, and Management. Springer Science and Business
Media; 2012.
3. Park  EA, Powers  GF. Acrocephaly and scaphocephaly with
symmetrically distributed malformations of the extremities:
A study of the so‑called acrocephalosyndactylism. Am J Dis Child
1920;20:235‑315.
4. Fishman  MA, Hogan  GR, Dodge  PR. The concurrence of
hydrocephalus and craniosynostosis. J Neurosurg 1971;34:621‑9.
5. Collmann H, Sörensen N, Krauss J, Mühling J. Hydrocephalus in
craniosynostosis. Childs Nerv Syst 1988;4:279‑85.
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S361
6. Francis  PM, Beals  S, Rekate  HL, Pittman  HW, Manwaring  K,
Reiff  J. Chronic tonsillar herniation and Crouzon’s syndrome.
Pediatr Neurosurg 1992;18:202‑6.
7. Golabi  M, Edwards  MS, Ousterhout  DK. Craniosynostosis and
hydrocephalus. Neurosurgery 1987;21:63‑7.
8. Thompson  DN, Hayward  RD, Harkness  WJ, Bingham  RM,
Jones BM. Lessons from a case of kleeblattschädel: Case report.
J Neurosurg 1995;82:1071‑4.
9. Collmann  H, Sörensen N, Krauss  J. Hydrocephalus in
craniosynostosis: A review. Childs Nerv Syst 2005;21:902‑12.
10. Cinalli  G, Renier  D, Sebag  G, Sainte‑Rose  C, Arnaud  E,
Pierre‑Kahn A. Chronic tonsillar herniation in Crouzon’s and Apert’s
syndromes: The role of premature synostosis of the lambdoid suture.
J Neurosurg 1995;83:575‑82.
11. Thompson DN, Harkness W, Jones BM, Hayward RD. Aetiology of
herniation of the hindbrain in craniosynostosis. Pediatr Neurosurg
1997;26:288‑95.
12. Sainte‑Rose C, LaCombe J, Pierre‑Kahn A, Renier D, Hirsch JF.
Intracranial venous sinus hypertension: Cause or consequence of
hydrocephalus in infants? J Neurosurg 1984;60:727‑36.
13. James  G, Thompson  DN. Cerebrospinal fluid hydrodynamics in
craniosynostosis. In: Cinalli  G, Ozek  M, Sainte‑Rose  C, editors.
Pediatric Hydrocephalus. Springer, Cham; 2018.
14. Rieping A. Zur pathogenese des turmschädels. Deutsche Zeitschrift
für Chirurgie 1919;148:1‑51.
15. Hoffman HJ, Hendrick EB. Early neurosurgical repair in craniofacial
dysmorphism. Neurovascular Surgery. Berlin Heidelberg: Springer;
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Long‑term outcomes in patients with treated childhood
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19. Di Rocco  F, Jucá CE, Arnaud  E, Renier  D, Sainte‑Rose  C. The
role of endoscopic third ventriculostomy in the treatment of
hydrocephalus associated with faciocraniosynostosis. J Neurosurg
Pediatr 2010;6:17‑22.
 Review Article

Access this article online

Quick Response Code:
Chiari 1 and Hydrocephalus – A Review
Himanshu Sharma1,2, Jeffrey M Treiber1,2, David F Bauer1,2

Abstract:
Chari 1 malformation, a radiologic finding of caudal cerebellar tonsillar displacement, has a clinical course that
Website: can range from benign to complications involving life‑threatening hydrocephalus. While the pathophysiologic
www.neurologyindia.com processes underlying this variation in outcome remain a matter of scientific debate, the clinical realities and
decision‑making conundrums that these patients pose require a coherent approach to this entity. In this review,
DOI:
we seek to highlight the various processes underlying the development of hydrocephalus in patients with Chiari
10.4103/0028-3886.332274
1 malformations. Hydrocephalus may occur as a cause, consequence, or in parallel with the development
of Chiari 1 malformation, and understanding the etiology of such hydrocephalus is critical to the treatment
of Chiari 1 malformations with associated hydrocephalus. We further discuss the literature pertaining to the
management of these patients and unify the current scientific thinking on Chiari 1 malformations with the extant
data on operative management of Chiari 1 to develop a structured and pragmatic approach to the diagnosis
and management of patients with Chiari 1‑associated hydrocephalus.
Key Words:
Chiari, Chiari decompression, Chiari malformation, foramen magnum, hindbrain, hydrocephalus, posterior fossa

Key Message:
The association between Chiari 1 malformation and hydrocephalus is not fully understood, but hydrocephalus
can be either a cause or consequence of Chiari 1 malformation.

C hiari 1 malformation (C1M) is commonly

defined as a caudal displacement of the
cerebellar tonsils exceeding 5 mm past the
foramen magnum.[1,2] This radiological finding
is seen in <1% of the adult and up to 4%
of the pediatric population [3‑5] and is rarely
symptomatic, with asymptomatic isolated C1M
having a relatively benign natural history.[6,7]
However, some patients with symptomatic C1M
also present with hydrocephalus, diagnosed
either before or after surgical decompression.
These complex C1M patients may constitute
up to 10% of symptomatic patients, and
they can present a diagnostic and treatment
challenge, with potentially life‑threatening
symptoms if inadequately treated. [8] Patients
with these “complex” CIM may co‑present
1
Department of with syringomyelia or craniovertebral junction
Neurosurgery, Baylor abnormalities, further complicating the treatment
College of Medicine, algorithm for these patients [Figure 1].
2
Department of
Neurosurgery, Texas The underlying etiologies of C1M continue to be
Children’s Hospital, debated and may include a diverse spectrum of
Houston, TX, structural problems, including crowding of the
United States posterior fossa due to hindbrain overgrowth,
hindbrain dysgenesis and developmental arrest,
Address for mismatch between neural and bony components
correspondence:
Dr. David F Bauer, This is an open access journal, and articles are distributed under the terms
6701 Fannin Street, of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0
Suite 1230.01, Houston, License, which allows others to remix, tweak, and build upon the work
TX ‑ 77030, United States. non‑commercially, as long as appropriate credit is given and the new
creations are licensed under the identical terms.
E‑mail: dfbauer@
texaschildrens.org For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com
of the posterior fossa, embryologic vascular
and cerebrospinal fluid  (CSF) hydrodynamic
perturbations, and a pressure differential
between the intracranial pressure and spinal
intrathecal pressure. [1] These etiologies are
often cited to play a role in the development of
hydrocephalus in the subset of C1M patients that
develop hydrocephalus, but the cause‑and‑effect
relationship between C1M and hydrocephalus
remains unclear, highlighting our incomplete
understanding of both processes. In this review,
we seek to articulate a paradigm by which
C1M with associated hydrocephalus can
be approached in order to provide clinical
decision‑making guidance when treating these
patients.
The prevalence of hydrocephalus in patients
with Chiari 1 malformations ranges from 6.5%
to 9.6%,[9,10] and comorbid hydrocephalus is an
independent predictor of morbidity following
surgical decompression.[11] Clouding the clinical
picture, the development of hydrocephalus
following Chiari decompression is a known
surgical complication, occurring in between
1% and 9% of operated patients in various
case series. [12‑14] Is hydrocephalus the cause
How to cite this article: Sharma H, Treiber JM,
Bauer DF. Chiari 1 and Hydrocephalus – A Review.
Neurol India 2021;69:S362-6.
Submitted: 06‑Jul‑2021 Revised: 06‑Sep‑2021
Accepted: 25‑Sep‑2021 Published: 11-Dec-2021

S362 © 2021 Neurology India, Neurological Society of India | Published by Wolters Kluwer - Medknow
 Sharma, et al.: Chiari 1 and hydrocephalus
Figure 1: Chiari 1 malformation with associated cervical syrinx
of CIM in some patients? Is hydrocephalus caused by
decompression, possibly by arachnoiditis from intradural
infection or blood products after duraplasty? Published
case series describe the need for post‑operative treatment of
hydrocephalus with endoscopic third ventriculostomy (ETV)
or ventriculoperitoneal shunt (VPS). Reasons for the treatment
of postoperative hydrocephalus in surgically treated patients
with C1M documented in the literature include an increasing
ventricular size, CSF leak, or pseudomeningocele; worsening
cerebellar tonsil herniation after decompression; and
uncontrolled headache. Authors have described treating CIM
headaches with a VPS without decompression and treating
hydrocephalus associated with CIM with decompression
and no direct treatment of the hydrocephalus. These varied
presentations and successful treatments make us pause when
thinking about this complex entity [Figure 2].
The relationship between hydrocephalus and Chiari
malformations was noted during its first description in 1891
by the Austrian pathologist Hans Chiari. He proposed that
elevated intracranial pressure from hydrocephalus directly
results in hindbrain herniation through the foramen magnum.[15]
This “pressure from above” theory was supported by a later in
utero study that demonstrated progressive hindbrain herniation
in patients with congenital aquaductal stenosis. [16] Based
on his theory, cerebrospinal fluid diversion was proposed
as the appropriate treatment. His initial theory has been
expanded upon by others, including Gardner and Williams,
who generalized this explanation into a hydrodynamic‑based
theory of C1M. This theory provides a useful framework for
understanding one subset of C1M patients with hydrocephalus.
In this group of patients, C1M arises as a secondary,
reversible phenomenon as a consequence of increased
intracranial pressure (ICP), often due to primary obstructive
hydrocephalus, potentially from a supra‑ or infratentorial mass
lesion. When primary hydrocephalus is the proximate cause
of C1M, CSF diversion is often proposed as a reasonable first
step in treatment.[9,13,17] Treating the hydrocephalus first in these
patients has several advantages.[18] It resolves elevated ICP,
which may resolve the C1M when the underlying etiology is
unclear; moreover, it may independently improve or resolve
resultant syringomyelia and can reduce the risk of suboccipital
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S363
a b
c
Figure 2: (a) A 1-year-old who presented with feeding difficulty was found to have
C1M and was treated with posterior fossa decompression with improvement.
(b) This patient re-presented 10 years later with headaches and emesis, and
was found to have hydrocephalus and syrinx. (c) He was then treated with redo
decompression and fourth ventricular stent, with radiographic and symptomatic
resolution. The patient eventually underwent occipital-cervical fixation for basilar
invagination (not shown).
decompression complications such as pseudomeningocele
and CSF leak. In some cases, it may resolve C1M symptoms,
obviating the need for decompression.[8,19]
The association between hydrocephalus and Chiari
malformations is more complicated than this theory suggests
because treatment and resolution of hydrocephalus fail
to improve hindbrain herniation or symptoms in many
patients. [20,21] These findings suggest the existence of a
distinct subset of patients in which hydrocephalus is either a
secondary phenomenon arising from C1M or an independent
entity. With regard to the former, in 1932, Dutch surgeon van
Houweninge Graftdijk advocated an alternative explanation
for hydrocephalus in patients with C1M. He hypothesized
that the herniated fourth ventricle outflow tract results in
cerebrospinal fluid flow obstruction and hydrocephalus.[22]
Logically, he advocated for the surgical correction of this
obstruction by widening the foramen magnum and occipital
cervical junction in a procedure now commonly referred to as
“Chiari decompression.” He hypothesized that the herniation
of the fourth ventricle outflow tract in C1M patients is the
primary pathology arising from a disproportion between
cerebellar volume and the total volume of the posterior fossa,
with the proximate cause of the hydrocephalus from CSF flow
obstruction at the fourth ventricle outflow in these patients.[23]
Recent support for this etiologic theory has been demonstrated
by studies utilizing flow‑sensitive phase‑contrast and cine‑phase
MRI sequences. Overcrowding of the foramen magnum by
cerebellar tonsils and brainstem does result in the obstruction of
CSF pulsation and flow at the foramen magnum.[24,25] These and
other studies examining the pathophysiology of syringomyelia
suggest that when CSF movement is obstructed at the foramen
magnum, the normal movement of CSF from the basal cisterns
into the spinal canal during cardiac systole is restricted and
accompanied by a simultaneous downward thrust of the cerebellar
tonsils, partially plugging the subarachnoid space posteriorly and
increasing the velocity of CSF into the narrowed outflow tract[26]
 Sharma, et al.: Chiari 1 and hydrocephalus
and creating pressure waves in the spinal subarachnoid space.[23]
These altered CSF dynamics resolve after decompression, and
many authors argue that hydrocephalus‑associated C1M in this
group of patients is “acquired, not congenital.” These alterations
in CSF egress, as well as pulse pressure, may contribute to
the development of hydrocephalus through obstructive and
hydrodynamic alterations.
While the fundamental underlying causes of C1M may be
varied, it is germane to consider several theories because there
are likely patients with C1M who develop hydrocephalus as
a secondary phenomenon, whose treatment should focus first
on the correction of the C1M as the hydrocephalus should then
secondarily resolve. One of the prevailing hypotheses relates
to cranialcephalo disproportion, in which the brain tissue
in the posterior fossa exceeds the volume of the intracranial
space allocated during development. This is proposed to arise
through many mechanisms, including imbalance between
supra‑(lateral ventricle) and infra‑(fourth ventricle) choroid
plexus pulsations in development leading to anatomic
changes to the posterior fossa, tentorium, and hydrodynamic
disequilibrium;[27‑29] dissynchrony of bony and neural element
growth (particularly as related to premature fusion of cranial
sutures—in particular, the lambdoid suture);[30‑35] and cerebellar
overgrowth [Figure 3].[36,37]
Examination of the pathophysiologic processes related to
C1M etiologies in patients with the second group revealed a
third process relevant to the development of hydrocephalus in
C1M patients—the development of jugular foraminal vascular
congestion and subsequent decreases in CSF resorption.
This mechanism, initially hypothesized by Hoffman and
Hendrick in relation to hydrocephalus associated with
craniofacial syndromes,[38] involves impaired venous outflow
leading to reduced CSF egress and increased ICP, which
may then contribute simultaneously to the development
of hydrocephalus and descent of cerebellar tonsils. Venous
hypertension would lead to decreased CSF resorption, cerebral
a b
c d
Figure 3: Newborn patient with chromosomal microdeletion, sagittal synostosis,
and tethered cord with a baseline MRI at birth (a) and at 18 months (b) that
demonstrates interval development of a Chiari 1 malformation. Patient underwent
endoscopic third ventriculostomy and shunt placement followed by Chiari
decompression (c). Despite this, patient continued to have refractory intracranial
hypertension and underwent cranial vault exapnsion (preoperative modeling shown
here; osteotomies to foramen magnum not shown) with resolution of symptoms.
S364 Neurology India | Volume 69 | Supplement 2 | November-December 2021
edema, and cerebellar engorgement, which would, in turn,
promote descent of tonsillar descent. Cinalli et al.[39] directly
demonstrated jugular foraminal stenosis with resultant
extensive venous collateralization in a series of Crouzon
and Apert syndromic patients with progressive C1M and
hydrocephalus. Further functional support for this hypothesis
comes from the resolution of hydrocephalus after jugular
foramen stenosis has been treated by direct jugular foramen
decompression with achondroplasia.[40] Other studies note
that in patients with achondroplasia, hydrocephalus and
its progression are correlated with venous sinus stenosis,[41]
though the relationship between the individual factors of
ventricular dilation, venous channel narrowing, foramen
magnum narrowing, and emissary vein enlargement have not
yet been well quantified.[42]
Previous authors[18] have suggested categorizing Chiari 1
malformation with hydrocephalus into groups based on their
pathophysiology. The first group includes hydrocephalus
with transient caudal descent. The second group is defined
as syndromic Chiari 1 malformations with hydrocephalus
from venous hypertension due to posterior fossa hypoplasia
and jugular foramina occlusion. The third group includes
nonsyndromic Chiari 1 malformations that have hydrocephalus
due to CSF under absorption from obstructed basal cisterns.
We appreciate this stratification of C1M patients as it is
undoubtedly important in guiding our understanding of and
research into the development of Chiari malformations. We
likewise propose categorizing Chiari 1 malformation‑associated
hydrocephalus into three groups in order to guide treatment
planning:
1. Hydrocephalus with secondary C1M
2. C1M with secondary hydrocephalus
3. C1M with concurrent hydrocephalus.
The first group includes the cohort of patients who have
primary hydrocephalus due to a variety of causes unrelated
to hindbrain herniation, including aqueductal stenosis or
mass lesions. These patients often benefit from treatment of
the underlying pathology[43,44] or primary CSF diversion.[8]
It is important to note that some of these patients may have
hydrocephalus due to altered CSF dynamics and resorption due
to fourth ventricular outflow obstruction. Clinically, however,
primary CSF diversion may improve their symptoms and thus
will benefit from the same treatment algorithm.
The second group is the subset of patients whose hydrocephalus
arises from the C1M itself. As discussed above, these patients
include those with cranialcephalo disproportion, which may
be due to a myriad of causes, one example being syndromic
craniosynostosis. These patients should not undergo CSF
diversion as the first method of treatment as CSF shunting
can exacerbate cranialcephalo disproportion[45] and even lead
to acquired C1M.[46] Most of these patients—in particular,
those with smaller posterior fossa to supratentorial volume
ratios—respond well to surgical treatments targeting the specific
pathology such as suboccipital decompression,[31] or cranial vault
expansion.[35] Our senior author’s bias is to include osteotomies to
the foramen magnum when performing cranial vault expansion
in order to adequately expand the posterior fossa and prevent
craniocephalo disproportion of the posterior fossa.
 Sharma, et al.: Chiari 1 and hydrocephalus
The third group may prove to be challenging to diagnose,
even with a thoughtful clinical approach. These patients have
radiographic findings of C1M, as well as hydrocephalus.
However, the two findings may both be secondarily related to
the increased ICP secondary to venous congestion. Alternately,
a subset of these patients may simply be presenting at the
earlier stages of their disease process. There is evidence
that patients with C1M and ventriculomegaly without
symptoms of increased ICP do well with only posterior fossa
decompression;[47] furthermore, it is true that the majority of
asymptomatic Chiari patients never need surgery. Nonetheless,
the only patients in one study evaluating the natural history
of asymptomatic Chiari 1 who progressed were those who
were also noted to have ventriculomegaly.[48] The optimal
clinical management of these patients remains uncertain. While
increased venous pressure may be implicated through vessel
imaging and direct venous decompression has been shown in
case reports as an effective treatment, there is no published
clinical guidance about a consistent method for diagnosing
such venous congestion, efficacy of this approach in treating
C1M, or the optimal timing of such treatment.
Our Clinical Paradigm for Treatment and Evaluation
When encountering a patient with CIM and hydrocephalus,
it is important to perform a thorough history and physical
examination and augment this with sufficient imaging to
make an educated guess as to the best initial course of action.
A general approach to the treatment of Chiari 1 malformations
with hydrocephalus is to treat the hydrocephalus with CSF
diversion (i.e., extraventricular drain (EVD), ventricular
shunting, or endoscopic third ventriculostomy) prior to
suboccipital decompression. We often take the approach
of placement of an EVD prior to decompression in these
patients, which allows postoperative CSF diversion and ICP
monitoring, if needed. If there is a mass lesion or obstructive
hydrocephalus from aqueductal stenosis, we treat these
entities first. If hydrocephalus arises from the fourth ventricle
outflow obstruction from the malformation itself, then surgical
decompression should result in resolution of hydrocephalus
without additional unnecessary CSF diversion procedures.
We rarely place a fourth ventricular stent. Patients with
CIM and hydrocephalus who continue to have symptoms of
hydrocephalus after CIM decompression typically undergo
ETV or ventriculoperitoneal shunt at our institution. Because of
the overlap in symptoms and varied etiology for hydrocephalus
and symptomatic CIM, a stepwise and thoughtful approach
is needed. We always discuss these varied scenarios with our
patients and families prior to the initial operation in order
to prepare them for the possible need for future additional
procedures.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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Pathogenesis of Chiari malformation: A morphometric study of the
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37. Martínez‑Lage JF, Guillén‑Navarro E, Almagro MJ, Felipe‑Murcia M,
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38. Hoffman HJ, Hendrick EB. Early neurosurgical repair in craniofacial
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malformation with syringomyelia secondary to colloid cyst
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Pettorini B, et al. The natural history of the Chiari type I anomaly.
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 Review Article

Access this article online

Quick Response Code:
Hydrocephalus in Spina Bifida
Jeffrey P Blount, Pedram Maleknia1, Betsy D Hopson, Brandon G Rocque,
W Jerry Oakes

Abstract:
Website: Hydrocephalus is the most important co-morbidity in myelomeningocele from a neurosurgical perspective.
www.neurologyindia.com Historically, 75-80% of patients with myelomeningocele have required treatment with a shunt but recent
DOI:
advances including intra-uterine myelomeningocele closure and ETV-CPC are reducing this burden. The
10.4103/0028-3886.332247 expression of hydrocephalus differs between patients and across the life span. Hydrocephalus impacts
the clinical expression of other important co-morbidities including the Chiari II malformation and tethered
spinal cord. Shunt failure is often the key stress to prompt symptomatic worsening of these other conditions.
Shunt failure may occur with minimal ventricular change on CT or MRI in Spina Bifida patients. Waiting for
radiographic changes in symptomatic SB patients with shunts may result in hydrocephalus related fatalities.
It is hypothesized but not proven that shunt failure may contribute to respiratory insufficiency and be a risk
factor for sudden death in adult patients with spina bifida. Excellence in hydrocephalus management in MMC
is essential for proper care, good outcomes, and quality of life for patients and families.
Key Words:
Hydrocephalus, ventricular shunt, endoscopic third ventriculostomy

Key Message:
Excellence in hydrocephalus management in MMC is essential for proper care, good outcomes, and quality
of life for patients and families. No other comorbidity is so central to neurologic well‑being or can affect so
many other processes.

M yelomeningocele is the most common

and most severe congenital anomaly
of the human central nervous system that is
This paper examines several key issues
surrounding hydrocephalus management in
children with open MMC:
compatible with life. Fundamentally, it is a 1. Impact of IUMC on hydrocephalus
neurologic disorder that arises from a failure in 2. Decisions surrounding delivery and
Division of Pediatric the closure of the posterior neuropore, which macrocephaly
Neurosurgery, leads to a myriad of structural anomalies of 3. Threshold for initial treatments‑ appropriate
Department of the nervous system, the most obvious being triggers
Neurosurgery, the exposed spinal placode on the back. [1] 4. ETV‑CPC vs. VPS as initial treatment
University of Alabama Impaired neurologic regulation of critical systems 5. Hydrocephalus and the C2M
at Birmingham, such as the renal/urogenital system and the 6. Hydrocephalus in childhood and adolescence
Birmingham, Al. musculoskeletal system imparts a wide range of 7. MMC hydrocephalus in adulthood
USA 35233, 1UAB secondary important comorbidities.[2] However,
School of Medicine, none of these comorbidities by themselves Impact of IUMC on hydrocephalus
University of Alabama have the far‑reaching impact of hydrocephalus. Intrauterine closure of myelomeningocele (IUMC)
at Birmingham, Hydrocephalus can be acutely life‑threatening has predominated most contemporary
Birmingham, Al. and can widely affect multiple other critical discussions and manuscripts related to MMC
USA 35233 neurologic comorbidities and conditions.[3] From management since the publication of the
a neurosurgical perspective, the management of Management of Myelomeningocele (MOMs) trial
Address for hydrocephalus is the “ground zero” for treatment in 2011.[5‑9] This randomized study prospectively
correspondence: in spina bifida.[2,4] Subtle declines in function compared children who underwent IUMC to
Prof. Jeffrey P. Blount, or insufficient drainage/decompression of the children who were managed with traditional
Department of
ventricles can stress an already compromised closure after delivery. IUMC was associated with
Neurosurgery, Division of
Pediatric Neurosurgery,
nervous system and promote amplified lower incidence of hydrocephalus, reduction in
Children’s of Alabama, downstream problems.[3] hindbrain herniation, and a higher functional
University of Alabama at
Birmingham, Lowder 400, This is an open access journal, and articles are distributed under the terms How to cite this article: Blount JP, Maleknia P,
1600 7th Avenue South, of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 Hopson BD, Rocque BG, Oakes WJ. Hydrocephalus
Birmingham ‑ 35233, AL, License, which allows others to remix, tweak, and build upon the work in Spina Bifida. Neurol India 2021;69:S367-71.
USA. non‑commercially, as long as appropriate credit is given and the new
creations are licensed under the identical terms. Submitted: 01‑Oct‑2021 Revised: 05-Oct-2021
E‑mail: Jeffrey.blount@ Accepted: 09-Oct-2021 Published: 11-Dec-2021
childrensal.org For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com

© 2021 Neurology India, Neurological Society of India | Published by Wolters Kluwer - Medknow S367
 Blount, et al.: Hydrocephalus in spina bifida
level than those who underwent post‑natal closure.[9,10] Only
60% of patients treated with IUMC required a shunt while
80% of those with post‑natal closure required a shunt.[11,12] The
study has galvanized the approach to MMC management.[6,7,10]
Within a few years, dozens of centers around the world had
developed programs for IUMC.[13] The cost of these centers
is high, and the procedure remains unavailable due to cost
and access for large numbers of affected pregnant women.
Nevertheless, the number of IUMC centers continue to expand
and considerable progress has been made toward reducing
morbidity, improving outcomes, and improving access to
IUMC.[7‑11,13‑15]
Hydrocephalus is favorably impacted regardless of techniques
of IUMC are utilized.[6,9]  Currently, only limited long‑term
follow‑up data are available. The threshold for treatment of
hydrocephalus may also be different following IUMC. Larger
ventricles may be tolerated after IUMC as opposed to
traditional post‑natal management.[11,14] Failure results in
shunt placement which is typically reserved for progressive
macrocephaly (>99% tile) with the crossing of percentile curves.
Whether larger ventricles will impact neurocognitive outcome
remains to be seen, but the earliest data is reassuring.[3,12]
Pregnancy delivery/macrocephaly
Approximately 2%–4% of fetuses affected with MMC
demonstrate pronounced in utero macrocephaly that may
promote the consideration of early delivery to treat the
hydrocephalus.[16,17] Such cases are rare, and most cases are
brought to term or near term.
Many obstetric teams prefer to deliver children with an open
MMC via cesarean delivery.[18] This is presumed to offer the
benefit of a more controlled, clean environment, and the
avoidance of bacterial inoculation of the placode arising from
the birth canal. Studies addressing this issue are varied in
their conclusions, and each have methodologic and design
limitations such that there is no clear propensity of evidence to
indicate superiority of either method of delivery.[17] However,
most obstetric practices have training preferences toward
cesarean delivery for MMC.[17,18]
Initial threshold for treatment of hydrocephalus
Traditionally, approximately 80% of babies born with
MMC go on to require placement of a shunt to control
hydrocephalus.[2,4,19] The decision for treatment is often obvious
due to macrocephaly, ventriculomegaly, or active CSF egress
from the closure site in the setting of a good surgical closure.[20,21]
Such cases require limited refinement in determining the need
for treatment, but preferences differ with regard to the timing
of shunt placement.[4,22,23]
When the child has obvious hydrocephalus, some pediatric
neurosurgeons prefer to place the shunt concomitantly with
the MMC closure.[23,24] With this approach, the CSF pressure is
removed from the closure site and the hydrocephalus is treated
promptly. Furthermore, the child is only anesthetized a single
time and the add‑on time for shunt placement is usually brief.
The disadvantage in some series is that shunt infections are
more prevalent, but no evidence is compelling.[25,26]
S368 Neurology India | Volume 69 | Supplement 2 | November-December 2021
Temporizing initial treatment
There has been a recent trend toward trying to temporize
hydrocephalus in less severe cases.[4] The idea is that some
children with MMC‑related hydrocephalus do not require
long‑term treatment if they can be temporized through the
perinatal period.[26] This typically requires tolerance of larger
ventricles/head size and more local wound care of the closure
and may require temporary diversion of CSF. Any child
demonstrating pronounced ventriculomegaly, rapid growth
trajectory, or any brainstem symptoms (e.g., stridor) undergo
treatment promptly. Utilizing these techniques, the incidence
of shunt placement was reduced to 65%.[26]
Other centers have temporized hydrocephalus with use of
external ventricular drains (EVDs) and subgaleal shunts and
have successfully but modestly reduced the incidence of the
need for a shunt.[4,22,27] Children with obvious ventriculomegaly
or brain stem signs were not temporized. Following 7–10 days of
temporary drainage the EVD is weaned and discontinued, and
the child is observed for signs of symptomatic hydrocephalus.
With these temporizing techniques the rate of shunt placement
was 68%, CSF dynamics were controlled immediately, and the
rate of back closure wound problems was reduced by more
than half.[26,27] However, complication rates of EVDs in small
babies is significant due to thin, fragile skin and stiff, robust
EVD catheters. Individual decisions must be made by the
treating surgeon or team with regard to practice preference
that take into account the best profile of risks and benefits with
temporizing measures in their individual experience.
ETV‑CPC vs. VPS as initial treatment
Another fundamental change that has occurred in the last
10 years in hydrocephalus management surrounds the role
of endoscopic third ventriculostomy with choroid plexus
cauterization (ETV‑CPC) as an alternate strategy to ventricular
shunts.[28,29] ETV‑CPC is covered elsewhere in this monograph
and will only be summarized here. Fundamentally, the procedure
incorporates an endoscopic third ventriculostomy combined with
endoscopic‑monopolar coagulation of at least 90% of the choroid
plexus.[29,30] It was developed and popularized by Warf et al.,
who initially reported a large experience utilizing ETV‑CPC in a
Ugandan cohort of infants with post‑infectious and MMC‑related
hydrocephalus.[30] Nuances and experience in the technique are
important, and the rate of plexus coagulation is critical. The rate of
success in the initial cohort exceeded 80% and eliminated the need
for a ventricular shunt. Subsequent studies by Warf et al. validated
these results in North American cohorts, but other teams have
struggled to attain such high success rates.[31‑33] Collective
data from the North American Hydrocephalus Research
Network (HCRN) has suggested an overall rate of success of
45%–50% for ETV‑CPC, but sub‑stratification of the outcome by
diagnosis has suggested better outcomes in children with MMC
as the etiology of hydrocephalus.[31]
The ventricles typically remain larger following ETV‑CPC
than with a ventricular shunt.[29,32] The definition of successful
treatment in ETV‑CPC does not require or anticipate small
ventricles. Rather, the trajectory of growth, calculated brain
volumes, and absolute head size are used to define success.
Whether modestly large ventricles are detrimental to long‑term
cognition is unknown, but the earliest evidence is favorable.[33]
Warf and Kulkarni reported equivalent modified Bayley III
 Blount, et al.: Hydrocephalus in spina bifida
development scores in the initial cohort of African children that
were followed for at least 3 years.[33] While these indices are
encouraging, more comprehensive assessment over a longer
time with bigger cohorts will be needed before a definitive
conclusion may be drawn.[4,20,33]
MMC hydrocephalus in infancy and childhood
Regardless of the choice of initial treatment for
hydrocephalus (ETV‑CPC vs. shunt), the critical parameters
to follow in MMC are identical. [20,22] Initially, concerns
center on wound‑related issues and signs of brainstem
dysfunction (symptomatic Chiari II malformation). They evolve
to focus on the rate of head growth and head size. The focus
on brainstem function is critical and remains primary to all
initial assessments of hydrocephalus. A useful fundamental
concept is that the Chiari II malformation is structurally
ubiquitous in MMC but is variable in its extent and clinical
expression. Post‑mortem histologic and cadaveric studies
in spina bifida demonstrate elongated, stretched brain stem
nuclei with gliosis and cell loss. Caudal displacement of the
cerebellar vermis occurs in Chiari II malformation (unlike
the cerebellar tonsils that are caudally displaced in Chiari I
malformations).  Collectively, these structural changes are
thought to impart a threat to normal brainstem function that
is variable in expression. It is likely that cellular and other
changes that are not readily imaged or visible (e.g. internuclear
axonal projection accuracy and efficiency) are variable and
contribute to brainstem dysfunction. Furthermore, myelination
is incomplete in infancy, which further challenges optimal
neuronal function.  As a result, brainstem function is threatened
and has a reduced margin of reserve to maintain airway support
and management of secretions. The C2M is a constant “weak
link in the chain.” CSF dynamics and control of hydrocephalus
appear to be the most important factor in alleviating the stress
of this compromised system. As such, subtle reductions in
control of hydrocephalus may prompt a decline in brainstem
function, which is threatening to the child.[4,22]
Brainstem dysfunction most frequently manifests as poor
secretion control and inspiratory stridor.[12,20] When occurring
during inspiration stridor reflects relaxation of the vocal cords,
expiratory stridor is more typically related to laryngeal anomalies
and impaired vocal cord formation. When cord contraction is
sufficient to nearly obstruct the airway the movement of air
across the nearly closed vocal cords creates an inspiratory,
high‑pitched, squeaking noise that is pathognomonic for
symptomatic Chiari II malformation. It also is a marker of a
critically threatened airway and mandates prompt and decisive
intervention. Hydrocephalus must be proactively controlled
when stridor is observed, and the child must be meticulously
observed for airway failure, hypoxia, increased work of
breathing, or other signs of airway obstruction and worsening
brainstem function. Some centers will perform shunt revision
while others will place an EVD.[20] There is no clear preferred
evidence‑based solution, but most centers revert to “tried and
true” interventions in the setting of stridor, opisthotonus, or
other critical signs of brainstem dysfunction.[20,22] The role of
posterior fossa decompression for Chiari II malformation is
also controversial, and there are significant disparities between
centers in thresholds for intervening. Initially, posterior fossa
decompression was thought central to salvaging a child with
symptomatic Chiari II malformation. However, modest success
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S369
from posterior fossa decompression coupled with significant
and often tragic surgical morbidity and mortality dampened
the enthusiasm for posterior fossa decompression and has
pushed most centers back to considering the critical intervention
directed toward controlling hydrocephalus.[20,22]
Once the child has demonstrated a satisfactory response
to treatment of hydrocephalus, he/she is followed as an
outpatient.[22,25,34] Families are coached and instructed on
the symptoms to observe for, which include generalized
fussiness, emergence of late stridor, increasing vomiting, and/
or arching and agitation. Wound‑related problems of either
the shunt/ETV‑CPC or initial back closure are also common
manifestations of hydrocephalus. The head growth curve
is followed over time and ventricular imaging is obtained
periodically with either fast sequence/quick brain MRI or CT.
For shunts, the arrest of head growth with reduction in ventricular
size to a new baseline is the objective.[27] For ETV‑CPC, reduction
in the growth trajectory to parallel the curve and stabilization
of ventricular size is the treatment objective. Failure of either
warrants further treatment. For ETV‑CPC, the critical assessment
pertains to repeating the procedure versus placement of a shunt.
For shunts, shunt exploration and revision remain the cornerstone
of treatment when dysfunction is diagnosed.
Overall shunts work well but are problematic in many
patients.[22] Approximately 50% of shunts fail within 2 years of
placement.  The average number of shunt revisions for children
with MMC‑related hydrocephalus in the United States Center for
Disease Control (US CDC)‑sponsored registry (National Spina
Bifida Patient Registry or NSBPR) between birth and age 18 is
3.2. However, some shunts function adequately for prolonged
periods and cumulative understanding of these better functioning
shunts is lacking. A high index of clinical suspicion must be
pursued, and shunt dysfunction must be treated aggressively.[25]
Hydrocephalus in childhood and adolescence
Management of MMC hydrocephalus in childhood and
adolescence is best considered a cooperative partnership
between the patient, family, and the treating team. Clear, open
communication and availability of professional assessment and
treatment are the cornerstones of successful care.[34] It must
be emphasized that shunt failure need not occur as an “all or
nothing” binary phenomenon and that mixed grades of shunt
insufficiency are seen commonly. As such, no single finding
is necessary to prompt a diagnosis of shunt failure and a high
index of suspicion and close, cooperative follow‑up over time is
essential.[35] The cardinal clinical trial of shunt failure, which is
headache, nausea/emesis, and sleepiness, may be present, but
many MMC patients will develop and demonstrate symptoms
unique to them, which must be observed, witnessed, and
acted upon to assure optimal support.[4,20,34] It is important that
patients and families understand that variability is common
and that they are not an oddity for manifesting symptoms other
than those considered classic for shunt failure.
Common symptoms of shunt dysfunction and hydrocephalus
decompensation vary individually, but common themes
emerge. Headache is the cornerstone symptom and varies
in expression with age. Infants often express fussiness and
irritability and are difficult to console. Older children and
 Blount, et al.: Hydrocephalus in spina bifida
adolescents may complain of headache that is coupled with
or predominated by neck pain. Neck pain in the setting of
shunted MMC‑based hydrocephalus is highly suspicious for
shunt failure. Often, the described symptoms involve pain at
the base of the skull that radiates into the neck, but the neck pain
may predominate. This clinical finding is important because
it is highly specific and may be missed by care providers
inexperienced in managing hydrocephalus in MMC.
Another symptom of shunt failure unique to MMC is low back
and hip pain. Symptoms imitate tethered cord syndrome, which
is an important comorbidity in MMC.[17] Characteristically, an
adolescent or child will complain of a low‑grade insidious
headache for weeks or months that is followed by progressively
severe lower back pain. Symptomatic tethered spinal cord
occurs in approximately 40% of patients with open MMC and
often requires surgical untethering for correction.[17] However,
impaired shunt function may imitate or precipitate tethered
cord symptoms sufficiently that many experienced surgeons
recommend shunt exploration before undertaking TSC release.
Spinal cord syrinxes may also be potentiated by impaired shunt
function. Symptoms may include pain in the neck and thoracic
region as well as a decline in hand function. Sensory decline
may produce negative symptoms of loss of pain, temperature,
and joint position or positive findings of progressively painful
dysesthesias. Over time, hand strength and coordination are
progressively impaired, atrophy ensues, and hand position
becomes dysmorphic because of neuropathic arthropathy. In
MMC shunt exploration, revision, and restoration of optimal
shunt function may arrest these findings.
The diagnosis of shunt failure in MMC may be supported
with imaging findings, but the clinical symptoms must remain
primary. Ventricular enlargement on CT or MRI scans in the
setting of clinical symptoms of headache, neck pain, or emesis
make the decision easier, but shunt failure commonly occurs
in MMC with little or no imaging change. Due to the fragile
brainstem function, it is entirely possible for MMC patients
to become severely threatened from shunt failure with little
or no accompanying image changes. As a result, a high index
of clinical suspicion for shunt failure and an awareness of the
broadness of clinical expression of shunt failure is essential in
caring for these patients.
Hydrocephalus in adult spina bifida
The literature on adult hydrocephalus associated with spina
bifida is scant.[36,37] Improvements in overall outcomes have
resulted in prolonged survival and an appropriate and
increased emphasis on adult and transitional care in spina
bifida.[35,38,39] Overall, it appears that the clinical course of
shunted hydrocephalus is less active and that fewer episodes of
shunt failure and shunt revision occur in adulthood, but these
observations are preliminary.[38‑43] Symptoms of shunt failure are
the same as those in childhood and center predominantly upon
progressively severe headache. The most common confounder
to the assessment of an adult with symptoms consistent with
shunt failure is presence of a urinary tract infection (UTI). Some
adults with UTIs will manifest with headache and malaise,
and these symptoms can imitate shunt failure. As such, the
evaluation for shunt failure in an adult with hydrocephalus
from MMC should include a catheterized urinalysis and urine
S370 Neurology India | Volume 69 | Supplement 2 | November-December 2021
culture. If these studies strongly suggest presence of a UTI and
the patient’s symptoms are modest and chronic, a course of
brief antibiotics may be considered prior to exploring the shunt
provided that the patient can be observed closely. UTI‑based
headache typically dissipates quickly with antibiotic treatment.
Furthermore, shunt revision in the setting of active UTI places
the patient at higher risk of a shunt infection. If symptoms
are severe, acutely progressive or include any brain stem
symptoms (swallowing or speech change), acute, prompt shunt
exploration is indicated even in the face of active UTI.
Conclusions
Excellence in hydrocephalus management in MMC is essential
for proper care, good outcomes, and quality of life for patients
and families. No other comorbidity is so central to neurologic
well‑being or can affect so many other processes. The Chiari II
malformation, spinal cord syrinxes, and tethered spinal cord are
critically important comorbidities that may become clinically
symptomatic in the setting of shunt failure. The expression
of hydrocephalus differs between patients and across the life
span. In infancy, brain stem function is critically dependent
upon good control of hydrocephalus. Patient‑specific symptom
complexes of shunt failure are common across childhood and
adolescence. Neck pain is common and ventricular changes on
imaging studies are often absent. New treatments including
ETV‑CPC and temporizing initial hydrocephalus are changing
important treatment paradigms and leading to reductions in
the prevalence of ventricular shunts. Spina bifida patients
are surviving into adulthood; thus, adult management of
hydrocephalus is increasingly important. Across the life span,
diligent attention to shunt function and a close, collaborative
relationship between the patient, the family, and the treating
team is essential for optimized care and outcomes.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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First 60 fetal in‑utero myelomeningocele repairs at Saint Louis
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effects of labor and delivery on spinal cord function and ambulation
in patients with meningomyelocele. Childs Nerv Syst 1991;7:312‑5.
18. Cuppen  I, Eggink AJ, Lotgering  FK, Rotteveel  JJ, Mullaart  RA,
Roeleveld N. Influence of birth mode on early neurological outcome
in infants with myelomeningocele. Eur J Obstet Gynecol Reprod
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19. Rocque BG, Hopson BD, Blount JP. Caring for the child with spina
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20. Blount  JP, Bowman  R, Dias  MS, Hopson  B, Partington  MD,
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21. Norkett W, McLone DG, Bowman R. Current management strategies
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22. Alford EN, Hopson BD, Safyanov F, et al. Care management and
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23. Ozgural O, Kahilogullari G, Dogan I, Eroglu U, Yakar F, Kilinc MC,
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reducing shunt placement rates in patients with myelomeningocele.
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27. McDowell MM, Lee PS, Foster KA, Greene S. The use of external
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28. Coulter IC, Dewan MC, Tailor J, Ibrahim GM, Kulkarni AV. Endoscopic
third ventriculostomy and Choroid plexus cauterization (ETV/CPC)
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29. Ellenbogen  Y, Brar  K, Yang  K, Lee  Y, Ajani  O. Comparison
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30. Warf BC, Campbell JW. Combined endoscopic third ventriculostomy
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31. Riva‑Cambrin  J, Kestle  JR, Rozzelle  CJ, Naftel  RP, Alvey  JS,
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 Review Article

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Quick Response Code:
Neurofibromatosis Type 1 Related
Hydrocephalus
Jonathan Roth1,2, Shlomi Constantini1,2

Website: Abstract:
www.neurologyindia.com
The prevalence of hydrocephalus among patients with neurofibromatosis type  I  (NF1) is estimated to be
DOI: between 1 and 13%. Aqueductal webs, chiasmatic‑hypothalamic tumors, and thalamic mass effect related to
10.4103/0028-3886.332254 NF changes are the common causes of NF1‑related hydrocephalus. Brain tumors and moyamoya syndrome
may mimic the clinical presentation of hydrocephalus in children with NF1, and should be ruled out while
evaluating children with headaches. Treatment of NF1‑related hydrocephalus should be personally tailored,
including shunts, endoscopic procedures such as septostomy and third ventriculostomy, and tumor resection
or debulking. Despite these personalized treatments, many of the primary treatments  (including shunts
and endoscopic procedures) fail, and patients should be screened and followed accordingly. In the current
manuscript, we review the causes of NF1‑related hydrocephalus, as well as treatment options.
Key Words:
Endoscopic third ventriculostomy, hydrocephalus, neurofibromatosis 1, optic pathway glioma, shunt

Key Message:
Neurofibromatosis type  1 related hydrocephalus is multifactorial. Most cases are obstructive due to
aqueductal webs or chiasmatic‑hypothalamic tumors. Treatment may include CSF diversion, endoscopic third
ventriculostomies, and tumor resections. Patients should be screened for recurrence of the hydrocephalic
process.

N eurofibromatosis type 1 (NF1) is the most

common neurocutaneous syndrome,
caused by an inherited or spontaneous
Etiology of NF1‑Related Hydrocephalus

NF1  patients are prone to develop obstructive

mutation in chromosome 17. The CNS hydrocephalus secondary to OPGs, other
manifestations of NF1 include tumors, such as CNS tumors, NF changes with a mass effect
optic pathway gliomas  (OPGs), non‑tumoral compressing the CSF pathways, and aqueductal
hamartomatous tissue changes (often classified stenosis.[4‑11] Causes such as an aqueductal web,
as “NF changes”), spinal neurofibromas, and periaqueductal gliosis, NF tissue changes, or
associated manifestations such as seizures and tumors in the midbrain  (including tegmental
hydrocephalus.[1] About 17–30% of NF1 patients or tectal regions), or unilateral thalamic
1
Department of
suffer from headaches, with most data originating masses, all lead to triventricular obstructive
Pediatric Neurosurgery,
from adult series.[2,3] This prevalence is similar to hydrocephalus [Figure 1].[4‑9,11‑14]
Dana Children’s
headaches among the general population.
Hospital, Tel‑Aviv
Medical Center, The actual pattern of hydrocephalus depends on
The incidence of hydrocephalus in NF1 patients the exact location of the obstruction. A unilateral
Tel‑Aviv University,
is estimated to be between 1% in adults and thalamic or basal ganglia mass may lead to
2
The Gilbert Israeli
13% in children. [3,4] The reason for the wide obstruction of the body of the third ventricle
International
incidence range may be related to different and obstruction of the foramina of Monro, or
Neurofibromatosis
NF1 populations, such as different age groups, may cause obstruction of the posterior third
Center GIINFC,
and whether patients were followed by ventricle and aqueduct, leading to triventricular
Tel‑Aviv, Israel
neurological/neurosurgical centers. hydrocephalus  [Figure  2]. A  large OPG,
Address for obstructing the third ventricle may lead to
correspondence: In the following manuscript, we overview obstruction of both foramina of Monro, leading
Dr. Jonathan Roth, the various etiologies of NF1‑associated to biventricular hydrocephalus [Figures 2 and 3].
Department of Pediatric hydrocephalus, as well as treatment options.
Neurosurgery, Dana
Children’s Hospital, This is an open access journal, and articles are distributed under the terms How to cite this article: Roth J, Constantini S.
Tel‑Aviv Medical Center, of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 Neurofibromatosis Type 1 Related Hydrocephalus.
6 Weizman Street, Tel License, which allows others to remix, tweak, and build upon the work Neurol India 2021;69:S372-5.
Aviv, 64239, Israel. non‑commercially, as long as appropriate credit is given and the new
creations are licensed under the identical terms. Submitted: 30‑May‑2021 Accepted: 25‑Sep‑2021
E‑mail: jonaroth@gmail.
Published: 11-Dec-2021
com For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com

S372 © 2021 Neurology India, Neurological Society of India | Published by Wolters Kluwer - Medknow
 Roth and Constantini: Neurofibromatosis type 1 related hydrocephalus
a b c
Figure 1: A 54‑year‑old patient resented with hydrocephalus secondary to a lateral
midbrain lesion known for many years (a). Following an ETV, the patient improved
and ventricles decreased; however, 3 years later he presented with hemiparesis
secondary to a tumor associated cyst (b). The cyst was endoscopically fenestrated,
and the patient is intact 4 years later (c). The solid component of the tumor is stable
for many years
Figure 3: A 10-year-old boy with a large OPG obstructing the foramina of Monro.
Coronal T2 weighted images. The child underwent a septostomy and a shunt.
Over the years he underwent various chemotherapy treatments, and eventually a
subtotal resection of the tumor (which was a pilocytic astrocytoma)
Prior surgery for other CNS‑related pathologies may
cause obstructive and non‑obstructive hydrocephalus. For
instance, prior surgeries for resection of upper cervical
neurofibromas may lead to local scarring of the fourth
ventricular outlet  –  leading to fourth ventricular outlet
obstruction  (FVOO), presenting with enlargement of all
four ventricles  [Figure  4]. Arachnoid thickening may cause
increased intracranial pressure.[15] Brainstem NF tissue changes
may lead to obstructive hydrocephalus too.
Thus, NF1‑related hydrocephalus is not a unified entity, but
a multifactorial condition, with many etiologies leading to
various types of hydrocephalus, most of which are obstructive
in nature.
Symptoms of NF1‑Related Hydrocephalus
Similar to hydrocephalus caused by any other etiology,
symptoms depend on acuity of hydrocephalus, age of patient,
and co‑morbidities.[11] Additionally, symptoms and signs
of increased intracranial pressure may overlap with other
NF1‑associated pathologies such as OPG, brain tumors,
and moyamoya syndrome. For instance, OPG in infants
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S373
a b
Figure 2: A 16‑year‑old girl with a large basal‑ganglia – thalamic tumor causing
obstruction of the foramina of Monro and compression of the third ventricle. (a)
Axial and (b) coronal T1 weighted with contrast images. She underwent a subtotal
resection (pathology was ganglioglioma grade I), followed by a shunt
Figure 4: A 36‑year‑old patient underwent resection of bilateral C2
kissing neurofibromas. He then developed fourth ventricle outlet
obstruction (FVOO) (figure) and underwent an ETV. However, the ETV failed and
he underwent a VPS a week later
may present with diencephalic syndrome, accompanied
by vomiting, even without the presence of hydrocephalus.
Additionally, visual decline may be secondary to OPG, and
not necessarily be related to hydrocephalus. However, a low
threshold for imaging should be maintained for children with
NF1 of all ages, to diagnose any associated pathology – be it
OPG (or dynamics in a known OPG), moyamoya syndrome,
other brain tumors, or hydrocephalus.
Diagnostic Modalities of NF1‑Related
Hydrocephalus
MRI is the modality of choice for evaluating headaches in
children with NF1. Apart from diagnosing hydrocephalus and
its causes, tissue changes associated with moyamoya should be
sought for (such as ischemic insults and IVY sign changes), and
MRA may be advised too in specific cases. Specific sequences
including T2 SPACE, CINE or FIESTA, and other protocols
enhancing obstruction in the aqueduct may be indicated,
similarly to non‑NF1 children presenting with hydrocephalus.
Gadolinium contrast is indicated at least at the initial scan – to
rule out tumors.
 Roth and Constantini: Neurofibromatosis type 1 related hydrocephalus
Spinal MRI is warranted in presence of hydrocephalus with no
obstructing culprit, to rule out a spinal tumor.
Treatment of NF1‑Related Hydrocephalus
Treatment of NF1‑related hydrocephalus may be focused
specifically on the cause of hydrocephalus, or on the
hydrocephalus itself.
NF1‑related OPG may be treated with chemotherapy, including
biological treatments such as BRAF or MEK inhibitors.[16,17] The
role of surgery in treatment of NF1‑related OPG is debatable,
and reserved for extensive tumors leading to significant mass
effect, or growing tumors despite medical treatments. OPG in
NF1 may lead to hydrocephalus through several mechanisms.
Local obstruction of basal cisterns will lead to enlargement of
all four ventricles. Obstruction of the third ventricle may lead
in some cases to obstruction of the foramina of Monro, causing
bilateral isolated hydrocephalus. These cases may be treated by
tumor resection (even partial)[18]; however, a shunt may be an
alternative option (coupled with a septostomy if the foramina
of Monro are obstructed), followed by chemotherapy.[10,19‑21]
Shunts for hydrocephalus associated with OPG have been
associated with increased risk of ascites, probably related to
secretion of protein by the tumors.[22] Endoscopic treatments
of OPG may include tumor biopsy, partial tumor debulking,
and fenestration of tumor‑related cysts.[18,23]
In cases with triventricular hydrocephalus, depending on
the anatomy of the third ventricular floor and the presence
of an OPG, an ETV is a valid treatment option. In a recent
multinational study, we found an ETV success rate of 76%
for selected patients with NF1‑related hydrocephalus.[6] ETV
may be performed for triventricular hydrocephalus even in
the presence of an OPG, if the OPG does not involve the third
ventricular floor. In selected cases, a trans‑stoma stent may be
recommended to maintain stoma patency.[6,24]
Thalamic NF‑related tissue changes are usually bilateral,
and may compress the third ventricle, causing bilateral
obstructive hydrocephalus with no obstruction of the Monro.
Hydrocephalus caused by unilateral thalamic lesions is usually
triventricular; however, as the compressing vector may
compress the body of the third ventricle too, this may affect
local anatomy and surgical considerations.[25]
Other etiologies for hydrocephalus among NF1 patients include
posterior fossa or cranio‑cervical compaction from tumors or
NF‑related hamartomas (NF changes), brainstem tumors, spinal
tumors, and postoperative conditions.[26,27] Despite the obstructive
nature of some of these conditions, ETV success rates are limited.
Despite the wide range of treatment options including
endoscopy or shunts, often in combination (such as adding a
septostomy, or inserting an Ommaya), our experience suggests
a high failure rate (60–71%) for a primary treatment – either
endoscopic or shunt procedures. Failure occurred in a bimodal
pattern, either during the first 6 months after surgery, or after at
least 3 years.[11] Thus, patients and families should be educated
to be aware of any new symptoms, and patients should be
screened for early detection of treatment failure.
S374 Neurology India | Volume 69 | Supplement 2 | November-December 2021
Currently, there is limited literature concerning treatment
paradigms. The causes of hydrocephalus in NF1 may be
multifactorial, thus, treatment is often multimodal, combining
treating the CSF aspects, tumor resection, chemotherapy, and
observation. Even after successful CSF treatment, the primary
etiology may continue to evolve, potentially affecting the
long‑term outcome.
Conclusions
Hydrocephalus in the context of NF1 is caused mostly
by obstructive etiologies. A  tailored‑treatment approach,
addressing the specific etiology, is recommended. Regardless
of the treatment approaches, a high rate of failures is described.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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12. Allen JC. Initial management of children with hypothalamic and
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14. Senveli E, Altinors N, Kars Z, Arda N, Türker A, Cinar N, et al.
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 Review Article

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Quick Response Code:
Hydrocephalus in Vein of Galen
Malformations
Srinivasan Paramasivam

Website: Abstract:
www.neurologyindia.com
Vein of Galen malformation (VOGM) is a fistulous arteriovenous malformation presenting in the early childhood.
DOI: Hydrocephalus with VOGM develops in one half of patients during the course of the disease. The concept of
10.4103/0028-3886.332279 hydrodynamic disorders is the key to understand the development of hydrocephalus. VOGM results in venous
hypertension that secondarily disturbs cerebrospinal fluid (CSF) absorption leading to hydrocephalus and
occurs frequently in infants and young children. The medullary veins are thought to be the main pathway for
absorption of CSF by the cerebrofugal gradient act as the driving force. In neonates, the cavernous sinus
is poorly developed and brain does not use it for venous drainage along with poor jugular bulb maturation
results in poor venous drainage reserve. The presence of high flow vascular malformation with poor venous
drainage reserve leads to hydrodynamic disorder, poor CSF absorption, and hydrocephalus. Apart from
this, hydrocephalus secondary to intraventricular hemorrhage and physical obstruction of the enlarged
VOGM at the aqueduct has been proposed. The management strategy is to perform timely endovascular
treatment to correct the hydrodynamic disorder and avoid ventricular shunting. Trans‑arterial embolization
is the effective way, as it decreases flow in the malformation, secondarily the venous hypertension, and
thereby improving the clinical symptoms related to hydrodynamic disorder. Ventricular diversion procedure
is indicated in symptomatic hydrocephalus after exhausting our effort to reduce hydrodynamic pressure by
endovascular embolization.
Key Words:
Hydrocephalus, hydrodynamic disorder, vein of Galen malformation

Key Message:
Hydrocephalus in presence of Vein of Galen Malformation is due to Hydrodynamic disorder. Reducing the
increased venous pressure is the key treatment strategy. CSF diversion is indicated for few selected cases.

V ein of Galen malformation (VOGM) is

a fistulous arteriovenous malformation
commonly presenting in the early childhood.
The fistulous high flow malformation is located
in the subarachnoid space in the choroid
fissure and embryologically related to the
development of the choroid plexus. In VOGM,
the arteriovenous fistulas drain into the persistent
embryonic precursor of the vein of Galen called
median vein of prosencephalon.[1,2] VOGM is
reported to represent less than l% of all AVMs
in the cooperative study of subarachnoid
Institute of hemorrhage. [3‑5] It is further classified into
Neurosciences, Apollo the choroidal type and the mural type.
Hospitals, Chennai, Hydrocephalus due to this high flow vascular
Tamil Nadu, India malformation is not uncommon and about one
half of them do develop during the course of the
Address for disease.[6] Pathophysiologic mechanism, clinical
correspondence: and radiological assessment, and management
Dr. Srinivasan
strategies are discussed in this chapter.
Paramasivam,
F1, 7/4 Habibullah
First Lane, Habibullah This is an open access journal, and articles are distributed under the terms
Road, T. Nagar, of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0
Chennai ‑ 600 017, License, which allows others to remix, tweak, and build upon the work
Tamil Nadu, India. non‑commercially, as long as appropriate credit is given and the new
creations are licensed under the identical terms.
E‑mail: kpsvasan@
hotmail.com For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com
Pathophysiology and Mechanism of
Development of  Hydrocephalus
To understand the development of
hydrocephalus in the presence of high flow
vascular malformation, one has to understand the
concept of hydrodynamic disorders. Zerah et al.[7]
were the first to recognize high venous pressure
as one possible cause of HC. In the presence of
VOGM, due to its fistulous nature, the flow is
very high resulting in venous hypertension that
secondarily disturbs cerebrospinal fluid  (CSF)
absorption leading to hydrocephalus. These
changes can occur in fetuses, neonates, infants,
and young children, but we see more commonly
in infants and young children.
The arachnoid granulations that are main channel
of CSF absorption in a matured brain are first
How to cite this article: Paramasivam S.
Hydrocephalus in Vein of Galen Malformations. Neurol
India 2021;69:S376-9.
Submitted: 13‑Jul‑2021 Revised: 21‑Jul‑2021
Accepted: 25‑Sep‑2021 Published: 11-Dec-2021

S376 © 2021 Neurology India, Neurological Society of India | Published by Wolters Kluwer - Medknow
 Paramasivam: Hydrocephalus in vein of Galen malformaitons
recognized only by 35 weeks after birth and continue to develop
throughout childhood. Before the development and maturation
of arachnoid villi, in neonates and infants, medullary veins
are thought to be the main pathway for absorption of CSF.
Ventricular CSF freely moves into the ependymal extracellular
space of the ventricular wall and drain through the medullary
veins. The negative pressure in the venous sinuses along with
positive pressure CSF pressure in ventricles create a cerebrofugal
gradient acting as the driving force for CSF absorption.
In neonates, the cavernous sinus is poorly developed and brain
does not use it for venous drainage. The cavernous sinus matures
later and sylvian veins connect to it several months after birth.
Until that time, all the venous drainage is through the centrally
located venous sinuses. In the environment of the physiologically
restricted venous drainage pattern, the presence of high‑flow
arteriovenous shunting results in venous hypertension causing
CSF malabsorption.[8] As the CSF malabsorption happens when
the skull bones have not fused, infants clinically manifest with
progressive enlargement of head with enlargement of sutures.
With progressive ventriculomegaly, intracranial pressure raises
and subsequently, developmental delay and mental retardation
sets in.
The venous sinuses do undergo modification after birth, and
most prominent of them is jugular bulb maturation. In the
presence of a high‑flow arteriovenous malformation, embryonic
venous sinuses such as marginal and occipital sinuses persist
resulting in halted maturation of the jugular bulb and sigmoid
sinuses. Subsequently, when embryonic sinuses close, the
immature sigmoid sinus and jugular bulb may be inadequate
to drain the brain and malformation. At this time, if the
cavernous sinus is developed well along with its connections
to cortical veins, the resultant venous hypertension will be
relatively mild. On the other hand, if the alternative pathway
for venous drainage of the brain is poorly developed, venous
hypertension will be overt and resultant clinical presentation
may range from hydrocephalus to seizures, hemorrhages, and
focal neurological deficits.[9] An interesting observation by
Mickle and Quisling, measuring the intraventricular pressure
and the pressure in the superior sagittal sinus (SSS) before and
after embolization of VOGM demonstrated a 5‑fold higher
pressure in the SSS than intraventricular pressure. They also
showed that the high pressure decreased dramatically after the
successful endovascular embolization of the VOGM.[10]
Hydrocephalus secondary to previous intraventricular or
subarachnoid hemorrhage due to scarring of the cisterns and
arachnoid granulation obstruction is well documented in the
literature.[11,12] Intraventricular hemorrhage either spontaneous
or following embolization procedure is managed in the acute
setting with external ventricular drain followed by ventriculo
peritoneal (VP) shunt if they develop persistent hydrocephalus.
Obstructive hydrocephalus due compression of the aqueduct of
Sylvius by the enlarged VOGM or space‑occupying coil masses,
embolic material, and organized clot filled malformation are
proposed as an alternate mechanism that can occur albeit rare.[6]
Progression to Brain Damage
In the presence of high‑flow vascular malformation, if
hydrocephalus left untreated or not so overt hydrocephalus
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S377
may cause subependymal atrophy and seepage of CSF along
the white matter fibers without further raise in intracranial
pressure. The resultant chronic venous congestion of
the brain induces calcification in the subcortical white
matter. There will be progressive brain atrophy resulting
in developmental delay in a child with initial normal
development. Such cerebral calcifications are diffuse,
subcortical, typically bilateral, and symmetric. The region
of calcification is considered the trans‑cerebral venous
watershed area between the superficial and deep venous
system. This venous watershed is relatively more superficial
than arterial transcortical water shed area. The location of
calcification is just beneath the cortical mantle. Development
of new onset subcortical calcification even with moderate
ventricular dilatation is suggestive of neglected chronic
venous congestion and progressive brain damage.
A more severe form of neglected hydrodynamic disorder
in children can result in severe brain damage resulting in
ex‑vacuo ventricular dilatation. Associated with VOGM, it is
called the melting brain syndrome and has been described in
detail by Lasjaunias et al.[8] Such brain changes can develop
relatively quickly and the brain damage is irreversible. In this
situation, neither the enlarged ventricles require drainage of
the ventricular system nor does the malformation require any
treatment.
Management of Hydrocephalus Related to VOGM
In any VOGM, though the final goal is complete obliteration
with normal development of brain without any focal
neurological deficit, the immediate treatment goal varies with
the age and presentation of the patient. The immediate goal in
neonatal period is to alleviate congestive heart failure. Beyond
the neonatal period, babies are watched carefully for the
development of hydrodynamic disorder. Close monitoring for
enlargement of head circumference, ventricular dilatation, and
for appearance of new subcortical calcifications is accomplished
by periodic regular follow‑up by pediatrician in bimonthly
intervals to assess head circumference and developmental
milestones. Radiographical assessment with noncontrast CT
scans is recommended at 6–10  weeks intervals, until about
5–8  months of age, when further endovascular treatment is
considered. If the head circumference progressively increases,
if developmental delay or milestone regression occurs, imaging
detects increased CSF spaces, subcortical calcifications, and
evidences of increased intracranial pressure; the management
strategy should perform timely endovascular treatment to
correct the hydrodynamic disorder and avoid ventricular
shunting. Trans‑arterial embolization is the effective way, as
it decreases flow in the malformation, secondarily the venous
hypertension, and thereby improving the clinical symptoms
related to hydrodynamic disorder. We avoid placement of a
ventricular shunt, in infants and children, by performing urgent
endovascular embolization in this situation. In a nutshell,
our treatment goal for infants and children is to restore the
hydrodynamic disorder to allow normal development of
brain [Figure 1].
Early ventricular shunting in the presence of hydrodynamic
disorder interferes with water balance between the extracellular
and intravascular compartments. It reverses normal pressure
 Paramasivam: Hydrocephalus in vein of Galen malformaitons

a b c d

e f g h
Figure 1: Antenatally detected VOGM baby on delivery was clinically stable with normal ventricular size (a). Clinical follow‑up showed rapid enlargemnt of head and CT
scan brain revealed enlargment of VOGM sac along with hydrocephalus at 4 months of age (b). Angiogram (c) and endovascular embolization done. Postprocedure CT scan
showed stable ventricles (d). One month later, CT scan revealed still larger ventricles, but head circumfernace remained stable (e). Subsequent embolization was done and
ventricles started shrinking (f). At the end of treatment, angiogram showed complete obliteration of malformaiton (g) and MRI revealed complete resolution hydrocephalus and
normal development of brain (h)

gradient from the ventricle to the superior sagittal sinus. This
causes brain edema and further enlargement of the dilated
draining vein of the VOGM and can predispose to rupture.
Other acute changes in the pressure gradient may induce
subdural hematoma and slit ventricles. In general, early VP
shunting is associated with poor outcome, and Schneider et al.
and other authors have experienced a 70% complication rate
associated with early shunting.[6,13,14]
The best management strategy is to reduce the venous
hypertension by early endovascular embolization to reverse
the hydrocephalus. When treated early, hydrocephalus is
prevented or treated without the need for placement of a
ventricular shunt. If endovascular treatment is delayed after
development of hydrocephalus, it becomes established and the
effect of embolization is usually insufficient and subsequently
ventricular shunt placement may become necessary even
after arteriovenous shunt and hydrodynamic disorders are
corrected. So, ventricular diversion procedure is indicated in
symptomatic hydrocephalus after exhausting our effort to reduce
hydrodynamic pressure by endovascular embolization.[10] In
this situation, following adequate endovascular embolization,
complications related to ventricular shunting are avoided.[4]
Third ventriculostomy may be an alternate option to ventricular
shunting for selected patients in the treatment of hydrocephalus
in combination with embolization.[8]
Conclusion
Hydrocephalus in patients with VOGM is not uncommon.
Understanding its pathophysiology, anticipation, and timely
treatment is essential for normal brain development. In
most situations, endovascular embolization to tackle the
hydrodynamic hydrocephalus is the sole treatment required.
VP shunting and third ventriculostomy are reserved for
few select persistent symptomatic hydrocephalus following
adequate obliteration of the malformation.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References
1. Berenstein A, Lasjaunias P. Modern concepts of Vein of Galen
Aneurysmal Malformation. Surgical Neuroangiography 3 Clinical
and Interventional aspects in Children. 2nd ed. Berlin Heidelberg:
Springer Verlag; 2006. p. 106-224.
2. Garcia‑Monaco R, Lasjaunias P, Berenstein A. Therapeutic
management of vein of Galen aneurysmal malformations. In:
Vinuela F, Halbach V, Dion J, editors. Interventional Neuroradiology:
Endovascular Therapy of the Central Nervous System. New York:
Raven Press; 1992. p. 113‑27.
3. Locksley HB, Sahs AL, Knowler L. SECTION II: General survey
of cases in the central registry and characteristics of the sample
population. J Neurosurg 1966;24:922‑32.
4. Sahs AL, Perret G, Locksley HB, Nishioka H, Skultety FM.
Preliminary remarks on subarachnoid hemorrhage. J Neurosurg
1966;24:782‑8.
5. Locksley HB. Natural History of Subarachnoid Hemorrhage,
Intracranial Aneurysms and Arteriovenous Malformations.
J Neurosurg 1966;25:321‑68.
6. Meila D, Grieb D, Melber K, Jacobs C, Maslehaty H, Petridis A,
et al. Hydrocephalus in vein of Galen malformation: Etiologies
and therapeutic management implications. Acta Neurochir (Wien)
2016;158:1279‑84.
7. Zerah M, Garcia‑Monaco R, Rodesch G, Terbrugge K, Tardieu M,
de Victor D, et al. Hydrodynamics in vein of Galen malformations.
Childs Nerv Syst 1992;8:111‑7.
8. Lasjaunias P, Ter Brugge K, Berenstein A. Introduction and general
comments regarding pediatric intracranial arteriovenous shunts. In:
Surgical Neuroangiography 3 Clinical and Inteventional Aspects in 
Children. 3. 2 ed. Berlin Heidelberg: Springer; 2006. p. 27‑104.
9. Andeweg J. Intracranial venous pressures, hydrocephalus and effects

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of cerebrospinal fluid shunts. Childs Nerv Syst 1989;5:318‑23. Syst 2010;26:35‑46.

10. Mickle JP, Quisling RG. The transtorcular embolization of vein of
Galen aneurysms. J Neurosurg 1986;64:731‑5.
11. Ebinu JO, Matouk CC, Wallace MC, Terbrugge KG, Krings T.
Hydrocephalus secondary to hydrodynamic disequilibrium in an
adult patient with a choroidal‑type arteriovenous malformation.
Interv Neuroradiol 2011;17:212‑6.
12. Geibprasert S, Krings T, Armstrong D, terBrugge KG, Raybaud CA.
Predicting factors for the follow‑up outcome and management
decisions in vein of Galen aneurysmal malformations. Childs Nerv
13. Jea A, Bradshaw TJ, Whitehead WE, Curry DJ, Dauser RC,
Luerssen TG. The high risks of ventriculoperitoneal shunt procedures
for hydrocephalus associated with vein of Galen malformations in
childhood: Case report and literature review. Pediatr Neurosurg
2010;46:141‑5.
14. Schneider SJ, Wisoff JS, Epstein FJ. Complications of
ventriculoperitoneal shunt procedures or hydrocephalus associated
with vein of Galen malformations in childhood. Neurosurgery
1992;30:706‑8.

Neurology India | Volume 69 | Supplement 2 | November-December 2021 S379

 Review Article

Access this article online

Quick Response Code:
Applications of Machine Learning in
Pediatric Hydrocephalus: A Systematic
Review
Bhavya Pahwa*, Ojasvini Bali1,*, Sarvesh Goyal2, Shweta Kedia2
Website:
www.neurologyindia.com

DOI: Abstract:
10.4103/0028-3886.332287
Introduction: Annually, hydrocephalus affects nearly 7 children per 10,000 live births around the world. It
significantly impairs the quality of life of such children and is associated with increased morbidity and mortality
The high cost of treatment and post‑intervention complications add to the burden of disease. Deployment of
machine learning (ML) models in actual clinical settings have led to improved outcomes.
Objective: The aim of this systematic review is to analyze the utility as well as acknowledge the achievements
of AI/ML in HCP decision making.
Methodology: PubMed and Cochrane databases were used to perform a systematic search with proper
terminology to include all the relevant articles up to May 2021.
Results: Fifteen studies that described the use of ML models in the diagnosis, treatment, and prognostication
of pediatric hydrocephalus were identified. The median accuracy of prediction by the ML model in various tasks
listed above was found to be 0.88. ML models were most commonly employed for ventricular segmentation
for diagnosis of hydrocephalus. The most frequently used model was neural networks. ML models attained
faster processing speeds than their manual and non‑ML‑based automated counterparts.
Conclusion: This study attempts to evaluate the important advances and applications of ML in pediatric
hydrocephalus. These methods may be better suited for clinical use than manual methods alone due to faster
automated processing and near‑human accuracy. Future studies should evaluate whether the use of these
models is feasible in the future for patient care and management in field settings.
Key Words:
Artificial intelligence, hydrocephalus, machine learning, neural networks, pediatric

Key Message:
Machine learning and artificial intelligence hold immense potential in improving the neurosurgical care and
management of pediatric hydrocephalus.

Medical Student,
University College
of Medical Sciences
A rtificial intelligence (AI) is one of the
most astonishing innovations of all
time. AI is “the theory and development
In neurosurgical care, the enormous quantity
of data warrants complex analysis including
preoperative mapping, intraoperative assistance,
and GTB Hospital, of computer systems able to perform tasks and postoperative survival.[5,6] ML models have
1
Medical Student, normally requiring human intelligence, such been found to surpass manual performance
Maulana Azad Medical as visual perception, speech recognition, in neurosurgical modalities, with a median
College, 2Department of decision‑making, and translation between absolute improvement in accuracy by 13%.[7]
Neurosurgery, All India languages.”[1] Machine learning (ML) allows Pediatric hydrocephalus (HCP) is a disorder
Institute of Medical computer algorithms to learn from experience of cerebrospinal fluid (CSF) metabolism
Sciences, Delhi, India without explicitly being programmed.[2] Data characterized by collection of CSF in the cerebral
explosion and increased computational power ventricles, leading to their expansion and an
*Shared first authorship make it possible to unleash the power of increased intracranial pressure. HCP affects
population data.[3] ML‑trained models are fed approximately 7.19 children per 10,000 live
Address for with input as well as desired output so that births.[8] High cost of treatment, lack of assurance
correspondence:
the final result is a predictive analysis of the of a good prognosis, and significant morbidity
Dr. Shweta Kedia,
Associate Professor,
unseen data.[2,4]
Department of How to cite this article: Pahwa B, Bali O, Goyal S,
Neurosurgery, All This is an open access journal, and articles are distributed under the terms Kedia S. Applications of Machine Learning in Pediatric
India Institute of of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 Hydrocephalus: A Systematic Review. Neurol India
Medical Sciences, License, which allows others to remix, tweak, and build upon the work 2021;69:S380-9.
Delhi ‑ 110 029, India. non‑commercially, as long as appropriate credit is given and the new
creations are licensed under the identical terms. Submitted: 11‑Sep‑2021 Revised: 29‑Sep‑2021
E‑mail: drshwetakedia@ Accepted: 10‑Oct‑2021 Published: 11-Dec-2021
gmail.com For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com

S380 © 2021 Neurology India, Neurological Society of India | Published by Wolters Kluwer - Medknow
 Pahwa, et al.: Machine learning and pediatric hydrocephalus‑A systematic review
and mortality additionally contribute to the burden of disease.
Use of ML algorithms in the management of HCP ranges from
estimation of CSF volume in the brain[9] to ventriculoperitoneal
shunt (VPS) infections prediction[10] and the requirement of
postnasal CSF diversion.[11] This systematic review aims to
analyze the utility of AI/ML in HCP decision‑making.
Methodology
Literature search
This systematic review was performed according to the
Preferred Reporting Items for Systematic Reviews and
MetaAnalysis (PRISMA) guidelines.[12] We screened PubMed
and Cochrane databases up to May 2021. Search syntax was
created [Supplementary Table 1] using the terms similar to
“Hydrocephalus” and “Machine Learning” along with Boolean
operators AND, OR, and NOT.
Inclusion and exclusion criteria
Search results included a vast array of studies ranging from
randomized controlled trials to cohort studies. The studies
included in this review:
1) Pediatric age‑group (0–18 years) patients
2) Only in English
3) Evaluated the application of ML in HCP care.
We excluded studies in which
1. No ML model was mentioned
2. No age group was mentioned/adults were the test set.
3. Inadequate information about the data sets
Data utilized from respective article included 1) year of
publication, 2) input type, 3) ML model, 4) application of
ML, 5) outcome, 6) training set, 7) test set, 8) validation set, 9)
validation method, and 10) performance.
Study selection
The search strategy retrieved 6632 results. The detailed
selection process is depicted in Figure 1. Following a full‑text
review, 15 studies were found to be eligible. Reference lists of
studies were manually searched to check if any potential study
was not captured by the search strategy. Selection of studies
and data extraction were performed independently by two
authors (B.P., O.B.). Fortunately, no disagreement was found
between the two authors.
Ratings of the quality of the evidence
We calculated TRIPOD adherence per item to report the quality
and evidence of studies included in the analysis [Figure 2].
Results
ML models were used in all aspects of HCP care and
management, that is, diagnosis, evaluating the need for
intervention, and for predicting the complications associated
with CSF shunting procedures. These models are described
briefly in Figure 3. ML was most frequently used as a diagnostic
modality [Figure 4]. Convoluted neural networks (CNNs)
and support vector machines (SVM) were the most popular
models [Figure 5]. Magnetic resonance imaging (MRI) was the
most commonly used input variable [Figure 6]. A summary of
the findings is given in Table 1.
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S381
ML in ventricular segmentation
Throughout the course of illness, patients with hydrocephalus
undergo numerous radiologic studies for clinical evaluation
and follow‑up. Manual segmentation, in addition to being
susceptible to human errors, is tiring and lacks generalizability
due to variations in imaging protocols and device specifications.
ML models can provide a rapid, objective, and unbiased
method for estimation of ventricular volume in patients with
hydrocephalus.
Seven studies used ML models for ventricular segmentation.
The CNN model was most frequently used for quantitative
estimation of ventricular volume.
Ono et al. [13] used a transfer learning (TL) approach in
conjunction with the 2.5D U‑Net for automatic segmentation.
Their proposed model outperformed conventional methods
(k means) and improved the DICE from 58% to 72%
(P value not mentioned). Using TL, they were able to use adult
data sets for estimation of infant ventricular volumes.
Quon et al. [14] compared the segmentation performance
of 2D U‑Net CNN to the FreeSurfer (FS) segmentation
platform. The U‑Net (DICE = 0.83 control, 0.94 for
hydrocephalus; t = 1.48 s/scan) model was more accurate
and faster than FS (DICE = 0.55 control, 0.86 for hydrocephalus;
t = 20.3 h/scan). Segmentation was more accurate in patients
with hydrocephalus  (Dice coefficient: 0.946) than in control
patients (Dice coefficient: 0.856).
Grimm et al.[15] compared segmentation performance of CNN
to the classical FAST algorithm. The results of the CNN‑based
segmentation (global accuracy: 0.89, Dice coefficient: 0.84) were
comparable to those of the FAST algorithm (global accuracy:
0.90, Dice coefficient: 0.87).
Klimont et al.[9] found that their U‑Net CNN model achieved
near‑human performance level (DICE score = 0.9506).
A “1 cycle” learning rate coupled with half‑precision training
enabled the authors to accommodate larger data sets within
the GPU memory.
Martin et al. [16] found that the fully convolutional
networks (FCN) such as U Net and V Net [U‑Net t = 3.5 ± 0.2,
Nvidia Tesla V100] are faster than the non‑FCN models
[t = 7454.2 ± 101.6 s, Nvidia Tesla V100]. Segmentation using 3D
FCNs were more accurate for normal ventricles (0.797 ± 0.041
against 0.776 ± 0.038), while for dilated ventricles, 2D FCNs
performed slightly better (0.893 ± 0.008 vs. 0.886 ± 0.004).
The 3D V‑net (Dice score t = 0.822 ± 0.053) was more
accurate than 2D U‑net (Dice score = 0.81 ± 0.062). However,
U‑Net was faster (t = 3.5 ± 0.2 s, Nvidia Tesla V100) than
V‑Net (t = 10.2 ± 0.2 s, Nvidia Tesla V100) irrespective of the
processor used. U‑Net may be more suitable for clinical use
because it can perform segmentation using graphic processing
units (GPUs) with much lesser processing power at higher
speeds. Compositional pattern producing network increased
the accuracy of the CNNs when they have fewer layers.
Li et al.[17] used support vector machine (SVM) to identify
children with hydrocephalus from normal controls, achieving
an accuracy of 88.46% (P  ≤  0.001). Thereafter, the SVM
 Pahwa, et al.: Machine learning and pediatric hydrocephalus‑A systematic review

Figure 1: Detailed process of selection of studies according to PRISMA guidelines

binary classifier based on grey matter measurements
classified hydrocephalus patients into two groups:
progressive hydrocephalus and chronic compensated
hydrocephalus (accuracy: 77.27%, P ≤ 0.009).
Cherukuri et al.[18] used the LC‑KSVD algorithm. Their model,
feature learning image segmentation (FLIS) [Brain 0.937 ± 0.21],
outperformed traditional intensity‑based methods, that is,
brain intensity segmentation (BIS) [Brain 0.58 ± 0.21]. FLIS
outperformed deep network for image segmentation (DNIS) in
a realistic training regime and was faster [69.83 s vs. 2860.66 s],
while DNIS was better when training was extensive (P < 0.01).
ML in Prognosis of HCP
The standard treatment for HCP is ventriculoperitoneal
shunt (VPS); however, in recent times Endoscopic third
ventriculostomy (ETV) has emerged as a novel alternative
treatment. Both methods are associated with complications
such as shunt failures and infections, which increase the cost
of treatment and adversely affect the patient’s quality of life.
Four studies evaluated the prognostic applications of ML in
HCP. Here, ANN was the most commonly used algorithm.
Hale et al.[19] compared ANN with conventional statistical
as well as four other ML approaches, namely SVM, k‑NN,
naive Bayes, and logistic regression. Younger patients,
etiology of hydrocephalus, longer duration of stay at
hospital, endoscopically assisted CSF shunt placement,
history of previous endoscopic third ventriculostomy, shunt
manufacturer, and use of an anti‑siphon device were found
to be statistically significant variables to predict shunt failure.
ANN (AUC = 0.71, specificity = 90%) outperformed the other
models to predict CSF shunt failure in pediatric patients.
Habibi et al.[20] drew a comparison between ANN and LR models
to predict the shunt infections in the form of a retrospective
study wherein birth weight, age at first shunting procedure,
numbers of shunt revision surgeries, history of premature
birth, myelomeningocele, intraventricular hemorrhage, and
coincided infections were used as input variables. The history
of shunt revision was found to be the most important factor.

S382 Neurology India | Volume 69 | Supplement 2 | November-December 2021

 Pahwa, et al.: Machine learning and pediatric hydrocephalus‑A systematic review
Figure 2: TRIPOD adherence per item calculated
ANN (AUC = 91.98%) superseded LR (AUC = 76.5%) in predicting
shunt infection in children with ventriculoperitoneal shunt.
Sabeti et al. [10] employed “feature selection” to reduce
dimensionality. The best selection was performed by genetic
algorithm (GA) and sequential feature selection (SFS).
Prematurity, intraventricular hemorrhage, age at first shunting,
number of shunt revisions, brain tumor association, birth
weight, and coinfection were predictive. Adaboost was the
most accurate ML model (AUC = 75.42 ± 8.41).
Azimi et al.[21] developed an ANN model with etiology, age,
whether choroid plexus cauterization (CPC) was performed,
previous shunt placement, sex, type of hydrocephalus, and
body weight in a group of children with hydrocephalus as
the input clinical features for predicting a successful ETV
outcome at 6 months. Performance of ANN was compared
to traditional predictive tools such as logistic regression, ETV
Success Score (ETVSS), and the CURE Children’s Hospital of
Uganda (CCHU) ETV Success Score. ANN had the highest
accuracy rate (93.7–97.6).
ML for determining the need for intervention
Interventions in HCP are associated with several complications
that increase the morbidity, mortality, and cost of treatment.
ML models can assess large quantities of clinical data and
radiological images, determine complex relationships among
these variables, and predict whether intervention is necessary
at the current clinical stage. This helps to streamline the
decision‑making process in HCP care.
We included four studies that used ML for determining
the need for intervention. One study developed a model
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S383
predicting the need for postnatal CSF diversion in
fetal ventriculomegaly. [11] Three studies [22‑24] predicted
posthemorrhagic hydrocephalus (PHH) and the need for
intervention.
Pisapia et al.[11] predicted the need for CSF diversion in two
cohorts‑ discovery and replication with the help of the SVM
algorithm. Linearity, area, and volume measurements from
fetal MRIs, and additional morphologic features were used
as training features for the model. The model successfully
predicted the patients who required CSF diversion with 82%
accuracy, 80% sensitivity, and 84% specificity. In the replication
cohort, the model improved with 91% accuracy, 75% sensitivity,
and 95% specificity.
A retrospective study by Obeid et al.[22] proposed that by
using early CUS of premature newborns with IVH, the
need for interventions to treat PHH can be easily predicted.
Morphological features, clinical variables, and a combination
of morphological and clinical variables were used to train three
separate predictive models—SVM, LR, and, SVM—and their
predictive accuracy was thereafter compared.
The model (SVM) using a combination of morphological
features and clinical variables showed the best results in terms
of accuracy (0.97) and P < 0.01 of predicting the need for a
temporizing intervention.
Tabrizi et al. [23] in 2017 used LR and SVM classifiers to
determine the need for intervention. SVM (sensitivity: 1.00,
specificity: 0.68, accuracy: 0.84) was more accurate than
LR (sensitivity: 1.00, specificity: 0.64, accuracy 0.82) and manual
measurement (accuracy: 76%, sensitivity: 1, specificity: 0.53).
 Pahwa, et al.: Machine learning and pediatric hydrocephalus‑A systematic review
a b c
d e f Figure 4: Utility of ML models‑ diagnosis, intervention, and prognosis
g h i in clinical practice.
Figure 3: ML models most frequently implicated in hydrocephalus. (a) NN
(ANN/CNN): An NN is composed of units or nodes called artificial neurons arranged
in layers connected to each other via synapse‑like connections called edges. These
nodes receive an input signal, processes it, and pass it on to succeeding neurons.
Signals travel successively through different layers getting transformed at every
step. (b) SVM: Support vector machine is helpful for classification, regression,
and other tasks such as outliers detection. To reduce the generalization error,
hyperplanes are built in a huge space so as to achieve a good separation from
the nearest points on either side. (c) LR: Logistic regression is a supervised ML
algorithm used for the classification of categorical input variables. It describes
a probabilistic value of 0 or 1 to the output. (d) RF: Random forests construct
innumerable decision trees. The output is the class selected by the majority of the
trees in classification tasks while, For regression tasks, the output is the average
prediction of the individual trees. Since they do not need much configuration while
predicting outcomes across large datasets, random forests are frequently used
as “blackbox” models. (e) kNN: K‑Nearest Neighbors estimates the distances
between an input and all the points in the data, selects the data points (k) closest
to the input, and determines the most frequent label (in the case of classification) or
averages the labels (in the case of regression). (f) NB: Naive Bayes is a supervised
algorithm that is based on the Bayes’ theorem used for probabilistic classification.
It is ‘naive’ because it assumes that every feature is independent of the other in the
pair for a particular value of the class variable. NB is extremely fast and requires
very little training. While it is an excellent classifier, this model may not be suitable
for estimation tasks because of its tendency to oversimplify the relationship among
the variables. (g) K‑SVD is popularly referred to as the “dictionary algorithm.” It
is a generalization of the k‑means clustering method. K‑SVD aims at minimizing
the error to a global minimum by combining the updated dictionary columns with
sparse representations. (h) Fuzzy C‑Means is an unsupervised learning algorithm
that clusters data points such that each data point is assigned a likelihood or
probability score to belong to a specific cluster. (i) Adaboost is mainly used to
improve the performance of other algorithms. The final output of this system is a
weighted sum, which is a combination of the output of the other learning algorithms
(weak learners)
However, LR needed fewer input features (n = 5) to achieve
the aforementioned accuracy as compared to SVM (n = 10).
The imaging parameter found to be most predictive of PHH
was the maximum value of medial axis lengths.
Tabrizi et al.[24] in 2020 used CNN to predict the progression
to PHH in premature neonates with IVH while a fuzzy
c‑means algorithm was used for image‑specific adaptation.
CNN (accuracy: 0.91 ± 0.08, P < 0.2) was less accurate than
manually based segmentation (accuracy 0.97 ± 0.06, P not
mentioned) but faster than the latter (t = 0.3 min vs. 3.22 min).
Imaging metrics had a higher predictive value than clinical
S384 Neurology India | Volume 69 | Supplement 2 | November-December 2021
variables (accuracy: 0.94 vs. 0.85; P < 0.001). Age in days at CUS
when IVH was first observed and GA in weeks and maximum
width of ventricles in mm were most predictive of PHH. The
average prediction time using CNN was 22 days earlier than
Discussion
Hydrocephalus is one of the most common pediatric
neurosurgical disorders. USA spends roughly US$2 billion
every year on care and management of hydrocephalus. [25]
Whether treated or not, HCP leads to complications in children
with hydrocephalus that hampers their quality of life. The
rapid advancement of AI and ML in the medical field can
lead to improved outcomes in not just hydrocephalus but
neurosurgical care as a whole. To the best of our knowledge,
this is the first review article to establish the significance of
ML in hydrocephalus.
A 2017 review article by Senders et al. [6] reported two
studies (Azimi et al. and Habibi et al.) that used ML methods
for prognostication in pediatric HCF. However, our study
conducted in the year 2021 describes 15 uses of ML tools in
not only prognosis but also diagnosis and intervention of HCP.
This is reflective of the staggering growth of ML in the field of
medicine and its immense potential to become an indispensable
clinical resource for physicians in the near future. Figure 7
depicts the number of studies done on a yearly basis in the
last decade to emphasize on the aforementioned statement.
Other uses of ML in neurosurgery
ML models have proved to be staggering tools in
a neurosurgical workflow comprising temporal lobe
epilepsy (TLE), glioblastoma multiforme (GBM), lumbar disk
hernia (LDH), lumbar spinal stenosis (LSS), arteriovenous
malformation (AVM), subarachnoid hemorrhage (SAH),
subdural hemorrhage (SDH), Parkinson’s, and traumatic brain
injury (TBI).
Lahmiri et al.[26] used intracranial EEG recordings and detection
rate as inputs for generalized Hurst exponent (GHE) and KNN
to differentiate the seizure from non‑seizure classes with a
100% accuracy rate. A review article mentioned the use of
ML in detection of epilepsy in a very vivid manner.[27] Many
studies[28‑31] have reported how GBM management and care
can be made better with ML predictive classifiers. Various
ML techniques are being developed to assess the complicated
genomic data with clinical and demographic data for getting
 Pahwa, et al.: Machine learning and pediatric hydrocephalus‑A systematic review
Figure 5: Most commonly used ML models
Figure 6: Variety of input variables used
Figure 7: Number of studies done on a yearly basis in the last decade
a more advanced insight into the pathogenesis of Parkinson’s
disease, diagnosis, and identifying potential biomarkers.[32‑38]
Identifying patients and predicting the surgical outcome of
discectomy and/or laminectomy is another area where ML is
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S385
successful.[39‑47] Predictive ML models can serve as a source of
assessment of SAH and related complications.[48‑56] ML has been
beneficial in the prediction of complications after stereotactic
radiosurgery for AVM[57,58] and differentiating AVM‑related
hematomas from other spontaneous intraparenchymal
hematoma types.[59] Not to mention, ML provides accurate
prognostic[60‑64] as well as patient identification[65‑68] classifiers
to support TBI.
Other uses of AI/ML in pediatric conditions
AI and ML have been well reported in innumerable pediatric
conditions. Liang et al. developed a natural language
processing‑based model that could accurately diagnose
several common pediatric complaints using electronic
health records such as acute upper respiratory infection,
acute asthma exacerbations), bacterial meningitis (0.93),
and infectious diseases such as influenza (0.94) and
varicella (0.93).[69] According to Reid et al.,[70] ML models have
been used for diagnosis of several pediatric ophthalmological
conditions such as retinopathy of prematurity, strabismus,
errors of refraction, classification of pediatric cataracts,
and prediction of postoperative complications surgery. ML
models assist biomedical diagnosis and imaging, clinical
decision making, drug development, and monitoring in
the field of pediatric cardiology. [71] Other areas where
ML tools have been used include pediatric radiology
(for image detection, classification, and segmentation), in
pediatric critical care (traumatic brain injury evaluation),[72]
pediatric nephrology (for estimating dry weight in chronic
hemodialysis),[73] and pediatric psychiatry (to assess the
association of high brain volume and the risk of developing
autism spectrum disorders).[74]
Future challenges
The future of ML in medicine holds great promise. However,
the development of deep learning faces several challenges.
Lack of availability of robust, high‑quality data hampers
research. The tendency of these models to get locked
into proprietary platforms may pose a problem. This will
hamper the process of transfer learning. Interoperability and
information exchange is of prime importance. Data ownership
issues—does the data belong to the patient, to the clinician,
the algorithm developer, or the community? How should the
stakeholder be compensated? There also exist issues with data
anonymization and data privacy. The traditional methods
of anonymization do not work well with large computing
systems that employ data mining techniques. The black‑box
approach: Interpretability of data is possible only in classical
machine learning. In deep learning, as we start moving
toward transfer learning, it is entirely possible that we may
not understand the means of getting to a conclusion. However,
we are still some distance from artificial superintelligence.
Therefore, it is imperative that we build ethics into the value
system of the machine. The control of the ML tools should
remain in the hands of humans.
There were some limitations to our study. Our study could
have been affected by selective outcome reporting and
publication bias. Because of heterogeneity in the included
studies, quantitative analysis was not feasible. Larger sample
sizes would likely have demonstrated additional significant
performance differences between algorithms.
 Pahwa, et al.: Machine learning and pediatric hydrocephalus‑A systematic review

Table 1: Summary of studies assessing the use of Machine Learning models in Pediatric Hydrocephalus care
Year Author Outcome Model Input Use Validation set Test set Training Prediction (% Quality of
and method Set accuracy/AUC) Evidence
2014 Azimi ETV success ANN Clinical Prognosis 42/‑ 42 84 0.86 (ANN) 2 Well-designed
et al.21 LR features 0.79 (LR) controlled
trial without
randomization
2016 Habibi VPS infection ANN Clinical Prognosis ‑/‑ 22 126 83.1%/91.98(ANN) 3 Retrospective
et al.20 LR features 55.7%/76.5(LR) case conr
2017 Tabrizi Predict PHH SVM, LR US Intervention ‑/LOOCV 36 28 0.84 (SVM) 3 Retrospective
et al.23 0.82 (LR) cohort
2018 Cherukuri Ventricular K SVD CT Diagnosis ‑/‑ 15 17 0.94 Could not be
et al.18 segmentation determined
2018 Pisapia Need for CSFSVM T2MRI Intervention 24/LOOCV 24 50 82% 3 Retrospective
et al.11 diversion case control
2019 Klimont Ventricular U‑Net/CNN CT Diagnosis 71/10‑fold cross 7 73 0.9506 2 Trial without
et al.9 segmentation [2D Unet] validation randomization
2019 Obeid Predict PHH SVM, LR US, Intervention ‑/15 fold CV Not Not specified 0.94‑0.97 (SVM) 3 Retro spective
et al.22 Clin specified Total 0.85 (LR)
62 (15+47)
2020 Ono Ventricular U‑Net FCN, MRI Diagnosis 6/LOOCV 6 30 0.72±0.11 3 Case control
et al.13 segmentation TL (Transfer
learning)
2020 Li et al.17 Ventricular SVM T1MRI Diagnosis ‑/LOOCV NA 22 88.46% 3 Case control
segmentation
2020 Grimm Ventricular HMM T2MRI Diagnosis 18/‑ 18 59 0.90 3 Retrospective
et al.15 segmentation cohort
2020 Tabrizi Predict PHH, U‑Net US Intervention 238/5‑fold & 62 953 0.91 3 Retrospective
et al.24 intervention CNN, fuzzy 15‑fold cross cohort
c‑means validation
2021 Martin Ventricular U‑Net, US, Diagnosis 3/4 fold cross 5 9 0.893±0.008 (2D FCN) Could not be
et al.16 segmentation V‑Net CNN MRI validation 0.886±0.004 (3D FCN) determined
[2D, 3D],
CPPN, FCN
2021 Quon Ventricular CNN [2D T2MRI Diagnosis 67/‑ 67 266 0.901 3 Case control
et al.14 segmentation Unet]
2021 Sabeti VPS infection NB, Clinical Prognosis 117/5‑fold cross 29 ‑ 66.90±6.72 (NB) 3 Case control
et al.10 prediction SVM, RF, features validation 63.45±9.93 (SVM)
Adaboost, 73.79±6.72 (RF)
kNN 75.42±8.41 (Adaboost)
68.97±5.4 (kNN)
2021 Hale CSF shunt ANN, LR, Clinical Prognosis 155/‑ 156 725 0.71(ANN) 2 Prospective
et al.19 failure kNN, ANN, features 0.613 (LR) 0.622 cohort trial
SVM, NB (kNN,5 neighbors) 0.647
(kNN, 10 neighbors)
0.689 (SVM) 0.670 (NB)
LC‑KSVD, Label consistent K‑singular value decomposition; kNN, k Nearest Neighbor; RF, random forest; LR, logistic regression; CNN/ANN, Convolutional neural network,
Artificial neural network; SVM, Support vector machine; HMM, Hidden Markov model; NB, Naive Bayes, Fully convolutional network; LOOCV, leave one out cross validation.
Quality of evidence assessment based on the modified Oxford Centre for Evidence-based Medicine for ratings of individual studies available at https://www.cebm.net

Conclusion Conflicts of interest

This study attempts to outline and present the important
achievements in this field and encourages clinicians to develop
other similar models that can revolutionize the management
of pediatric hydrocephalus. By extrapolating the approach of
studies already available in the literature on larger, diverse
sample sizes and under different scenarios, it may be possible to
develop models that can be deployed in actual clinical settings
to arrive at additional, yet unfound conclusions.
Financial support and sponsorship
Nil.
There are no conflicts of interest.
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Neurology India | Volume 69 | Supplement 2 | November-December 2021 S389

Supplementary Table 1: Subject
Subject Key terms
Machine learning MeSH Terms
Artificial Intelligence
Deep Learning
Machine Learning
Neural Networks
Support Vector Machine
Within Title/Abstract
Artificial Intelligence
Bayesian Learning
Computational Intelligence
Computer Reasoning
Deep Learning
Machine Learning
Naive Bayes
Natural Language Processing
Neural Networks
Random Forest
Support Vector Machine
Hydrocephalus MeSH Terms
Hydrocephalus
Pediatric
Endoscopic Third
Ventriculostomy
Ventriculo Peritoneal Shunt
Title/Abstract
Hydrocephalus
Filters applied Exclude-
Case Report
Comment
Letter to Editor
Review Article
 Review Article

Access this article online

Quick Response Code:
Pediatric to Adult Hydrocephalus:
A Smooth Transition
Manilyn A. Hong, Arvind Sukumaran, Jay Riva-Cambrin

Website: Abstract:
www.neurologyindia.com
Introduction: Pediatric patients treated for hydrocephalus, regardless of etiology, require continuous access
DOI: to care to address the long‑term sequelae from the disease progression itself and from the interventions
10.4103/0028-3886.332245 undertaken. The challenge for all pediatric neurosurgeons is providing comprehensive and coordinated care
for these patients in order to achieve a smooth and seamless transition into adult health care.
Methods: A review of the literature was conducted regarding the overall concept of pediatric patients with chronic
conditions transitioning to adult care. We also specifically reviewed the pediatric hydrocephalus literature to
investigate the barriers of transition, models of success, and specific elements required in a transition policy.
Results: The review identified several barriers that hamper smooth and successful transition from pediatric
to adult care within the hydrocephalus population. These included patient‑related, cultural/society‑related,
healthcare provider‑related, and healthcare system‑related barriers. Six elements for successful transitions
were noted: transition policy, tracking and monitoring, transition readiness, transition planning, transfer of
care, and  transition completion stemming from the Got Transition center.
Conclusions: A successful patient transition from pediatric neurosurgical care to adult neurosurgical care
is very center‑specific and depends on the available resources within that center’s hospital, health system,
and geo‑economic environment. Six recommendations are made for transition policy implementation in
resource‑poor environments, including beginning the process early, preferably at age 14 years.
Key Words:
Hydrocephalus, pediatric neurosurgery, transition to adult care

Key Message:
Transitioning pediatric hydrocephalus children to adult care is critical and possible in both resource-rich and
resource poor countries. Optimally, it should begin at around age 14, follow the Got Transition process, but
adapted to the specific geo-economic environment.

H ydrocephalus results when there is a

disturbance in the production, flow,
or absorption of cerebrospinal fluid (CSF),
requiring surgical intervention,[7] with long‑term
outcomes varying according to etiology.

causing excessive accumulation of CSF in Why is There a Need for Smooth

the ventricular system of the brain. [1] In the Transition from Pediatric to Adult  Care?
pediatric population, it can be congenital,
myelomeningocele (MMC)‑related, Advances in medical, surgical, and overall
brain tumor‑related, or as a sequela of pediatric care have resulted in increased
intraventricular hemorrhage (IVH), infection life expectancy for pediatric hydrocephalus
Department of Clinical (bacterial, tuberculous), or trauma.[2‑6] patients as many more children live into
Neurosciences, adulthood [2,8,9] and, therefore, requiring
University of Calgary, The global prevalence of pediatric continuing neurosurgical care. [3,6,10] These
Calgary, Alberta, h y d r o c e p h a l u s i s 8 8 / 1 0 0 , 0 0 0 , [5] w i t h advances have transformed hydrocephalus into
Canada lower‑income countries having a significantly a chronic condition worldwide.[5,11,12]
higher incidence (123/100,000) compared
Address for to high‑income countries (79/100,000). [7] Treated patients with hydrocephalus require
correspondence: Approximately 400,000 new cases per year of continuous access to neurosurgical care as
Dr. Jay Riva‑Cambrin, pediatric hydrocephalus develop worldwide endoscopic third ventriculostomies (ETVs)
Department of Clinical
Neurosciences, Alberta This is an open access journal, and articles are distributed under the terms How to cite this article: Hong MA, Sukumaran A,
Children’s Hospital, 28 of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 Riva-Cambrin J. Pediatric to Adult Hydrocephalus:
Oki Drive NW; Calgary, License, which allows others to remix, tweak, and build upon the work A Smooth Transition. Neurol India 2021;69:S390-4.
Alberta, T3B 6A8, Canada. non‑commercially, as long as appropriate credit is given and the new
creations are licensed under the identical terms. Submitted: 23‑Sep‑2021 Revised: 25‑Sep‑2021
E‑mail: jay.rivacambrin@ Accepted: 27‑Sep‑2021 Published: 11-Dec-2021
ucalgary.ca For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com

S390 © 2021 Neurology India, Neurological Society of India | Published by Wolters Kluwer - Medknow
 Hong, et al.: Transition in hydrocephalus care
and, especially, shunts notoriously fail.[3,9,10,12] These failures
can cause acute, life‑threatening neurologic deterioration
and further long‑term disability.[13] In one study, the overall
incidence of shunt failure in adult patients with pediatric‑onset
hydrocephalus was 82.9%. [14] Common causes of failure
include obstruction, infection, mechanical disconnection, and
over‑drainage.[3,11,14]
The American Academy of Pediatrics (AAP) defined the
goal of transition in health care for young adults with special
health care needs as “maximizing lifelong functioning and
potential through provision of high‑quality, developmentally
appropriate health care services that is uninterrupted from
adolescence to adulthood.”[10,15] The gold standard of care
should thus be a smooth, seamless transition[9,10] initiated at,
ideally, 14 years of age.[10,16] Failure of proper transitioning
can lead to increased morbidity, necessitate emergency
interventions, increased hospital admissions, and prolonged
hospital stays.[9,13] Therefore, failure to transition properly
translates into increased downstream healthcare costs; the
impact of which can be further exaggerated in resource‑poor
countries.
The majority of patients with pediatric‑onset hydrocephalus
remain shunt‑dependent throughout their lifetime,[14] with only
a minuscule proportion who later become shunt‑independent.[3]
Many are complex cases and may have undergone multiple
surgeries. The need for long‑term, preferably multidisciplinary,
follow‑up of pediatric patients with hydrocephalus after they
reach adulthood is established.[8,11,14] This is most evident in
high‑income countries’ (HIC) health care systems where many
processes and policies are already in place.[3,10] However, in
a country like India, the literature, processes, and policies
on transition are scarce and there is no universally accepted
model.
What are the Barriers to Transition?
The patient‑related barriers to successful transition include
poor compliance, fatigue, and lack of independence.[8,9,13,17]
Poor patient compliance stems from misinformation and can,
many times, be remedied by early education of both the patient
and the caregivers.[13,17] In terms of fatigue, often patients and
caregivers can become exhausted and frustrated with their
situation and may become “resigned to their fate.” This issue is
much more complex but probably can be mitigated somewhat
by educating patients and families regarding technological and
medical advances, such as ETV+CPC[18,19] and shunt infection
protocols,[20,21] that have positively impacted both longevity
and the quality of life of patients with hydrocephalus. These
successes breed hope for all income categories which, in turn,
can counteract fatigue and encourage perseverance. Finally,
an issue raised in a survey of pediatric neurosurgeons was
that patients were too “babied” in pediatric care, which may
undermine their ability to take ownership of their condition
and hamper their transition into adult care.[9] That survey
intimated that adolescents may rely too heavily on their
parents, family, or friends, and, thus, lack the independent
skills to fully understand and make decisions for themselves.
This concern is the very reason why a formal transition scheme
to adult care is so important and that it should be a process
that begins at an early age.
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S391
Cultural and societal barriers, especially in low‑ and
middle‑income countries (LMICs), play a role in hampering
transition, especially in the form of noncompliance. An example
of this type of barrier is that some cultures and religions
ascribe sickness to “God’s will” and demand minimal medical
interference. Another example would be extreme poverty
as direct and indirect costs of out‑of‑pocket health care can
constitute significant financial barriers to families especially
in, but not limited to, LMICS.[17,22] Seeking medical attention
directly affects a family’s income with time off work along
with significant associated transportation costs. In either
case, patients or families may not pursue further treatment or
care after the initial shunt especially as the child grows into
adulthood.
Healthcare provider‑related barriers to transition are the lack
of resources as well as, in many cases, the unwillingness of
adult‑centric neurosurgical providers to assume the care of
these comorbid adolescents.[9,13] As stated previously, these
patients can be complex and require more multidisciplinary
communication and cooperation. Therefore, they represent,
per capita, a heavier clinical load in terms of provider time
while, counterintuitively, are frequently poorly renumerated.
This paradox makes this patient population less attractive
to busy adult neurosurgeons and leaves fewer options for
neurosurgical providers for transition. Specifically, in LMICs,
the treatment of these hydrocephalus patients requires that all
the surgical options appropriate to their condition are available
to them,[2] which might not be entirely feasible in these countries
due to lack of adequately trained personnel.[22]
Healthcare system‑related barriers to transition exist in the
form of the lack of adequate financing, appropriate treatment
facilities (clinic space, complex nursing, etc.), and lost patient
records.[3,13] Electronic health records are not the norm in LMICs
but are highly recommended to aid in transition.[10] Lastly, just
the sheer overall lack of medical and surgical specialists is
probably the greatest system‑related factor aggravating poor
transition to adult care in LMICs.
What are the Models for Transition?
The transition from pediatric to adult practice is
dependent on local resources and healthcare organizations
(universal healthcare versus out‑of‑pocket health care). For
high‑income countries, pediatric and adult practitioners
would be linked to provide a seamless transition,[9,16] such
as in the University of Calgary: Adult Hydrocephalus
Clinic.[2] There can also be a hybrid or joint hydrocephalus
service, manned by both adult and pediatric neurosurgeons,
providing comprehensive care to all patients.[2,8] Generally,
in LMICs (e.g., India, the Philippines, and others) where the
number of specialists is scarce,[22] general neurosurgeons
manage both pediatric and adult hydrocephalus patients.
Therefore, patients are managed by disease‑specialty instead
of by age, and, often, no transition occurs.[2]
The multidisciplinary spina bifida clinics at many major
Western neurosurgical centers are excellent examples within
the neurosurgical sphere of a successful health care transition
model. Many have been thriving and have proven to be very
effective.[2,8,23‑25] This program involves specialties such as
 Hong, et al.: Transition in hydrocephalus care
neurosurgery, urology, orthopedic surgery, physical therapy,
orthotics, and other services such as social workers working
together for the patient. These clinics found that specialists
worked closely with each other, that an earlier age at
preparation for transition was optimal,[10,16] that patients were
more empowered and in control, and that both patients and
caregivers have had a positive experience during the process.[23]
Comprehensive and coordinated clinical care is the standard
for a smooth and seamless transition.[10]
What are the Elements of a Successful Transition
Program?
Health care transition is the process of moving from pediatric
to adult healthcare, with or without transferring to a new
clinician or health care provider. [26] There are six core
elements of a successful health care transition [Figure 1].
This was first conceptualized after the publication of the
2011 clinical report on healthcare transition by the American
Academy of Pediatrics, the American Academy of Family
Physicians, and the American College of Physicians.[27] The
framework shown in Figure 1 was developed by a federally
funded national resource center, Got Transition®,[23,26] and
was designed to be used by clinicians caring for young
adults during the health care transition process. The “Six
Core Elements of Health Care Transition” is a structured
process that can be customized to different settings, such as
transitioning a pediatric patient to an adult care clinician,
transitioning to adult care without changing clinicians, or
integrating patients into a completely new adult health care
system.[23]
The six elements are transition policy, tracking and monitoring,
transition readiness, transition planning, transfer of care, and
transition completion.[23,26,27] These have also been included in
the consensus statement of the American Society of Pediatric
Neurosurgeons [28] and the Hydrocephalus Association
Transition Summit, which is a large advocacy group for
hydrocephalus patients and their families.[29]
Figure 1: Got transition model for health care transition
S392 Neurology India | Volume 69 | Supplement 2 | November-December 2021
Best Practices Recommendations for Pediatric
Neurosurgeons for Successful Transition of
Hydrocephalus Patients to Adult Care That Can be
Applied in Resource‑Poor Settings
1. Pediatric neurosurgeons should have a written transition
policy in conjunction with adult practitioners based on a
model most suited to their clinical setting (transitioning a
pediatric patient to an adult care clinician, transitioning
to adult care without changing clinicians, or integrating
patients into a completely new adult health care
system).[28,29]
2. Pediatric neurosurgeons should start the transition process
in a timely fashion to allow for adequate patient preparation
and empowerment; based on our review, it should start at
14 years of age.[10,15,16,29]
3. Pediatric neurosurgeons should work with family doctors
and other members of the health care team to develop a
transition plan. Each members’ responsibilities should be
clearly delineated in the written transition policy.[15,28] This is
the medical home model[16,26,30] where all stakeholders work
together to provide comprehensive and compassionate care
centered on the patients’ needs throughout all stages of life,
integrated with other health services.
4. Pediatric neurosurgeons should assist in choosing the
appropriate adult care provider for the patient[15,16,28] or
have a joint hydrocephalus clinic with an adult provider
for continuity of care.[2,8,10]
5. Pediatric neurosurgeons should update either the paper
chart or the electronic health record prior to formal
transition. This documentation should include clinical
history and surgeries, recent imaging, details of how the
patient presents during shunt malfunction or ETV failure, as
well as a protocol for emergencies and follow‑up.[3,9,10,12,15,16,28]
This will bridge the communication gap between pediatric
and adult providers. This formal record should also be
provided to the patient and/or caregivers in case of a
geographical move or a change in medical or health care
system providers.
 Hong, et al.: Transition in hydrocephalus care
6. Pediatric neurosurgeons should seek feedback on the current
transition process from their multidisciplinary partners
and the patients themselves. A continuous assessment
and update of best practices to make improvements and
innovations in transition care can ensure optimal outcomes
in any resource setting.[23,26,28,29]
Conclusions
Many adolescent patients view health care as a low‑priority
aspect compared to other aspects of their transition to
adulthood (education, employment, independence, etc.). In the
hydrocephalus setting, these patients should be empowered to
maintain their health and continuing their care to maximally
achieve their life goals.[26] The problems they face during their
transition from childhood to adulthood are complex,[13] and any
recommendation put forth must consider input from them, their
families, and the medical and allied health care providers caring
for them.[8‑10] Detailed review into the needs of hydrocephalus
patients must be done based on the local setting in order to
develop formal guidelines and standards most suited to the
patient population and maximizing resource utilization.[10,28]
Health care transition for pediatric hydrocephalus must be
done in a formal, center‑specific, and comprehensive manner
lead by both pediatric and adult neurosurgeons.[3,13]
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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S394 Neurology India | Volume 69 | Supplement 2 | November-December 2021

 Review Article

Access this article online

Quick Response Code:
A Comparison of Adult and Pediatric
Hydrocephalus
Chandrashekhar Deopujari1,2, Chandan Mohanty1,2, Harshal Agrawal2, Sonal Jain2,
Pawan Chawla2

Website:
www.neurologyindia.com
Abstract:
DOI: Hydrocephalus is a common clinical problem encountered in neurosurgical practice. With greater
10.4103/0028-3886.332283 subspecialisation, pediatric neurosurgery has emerged as a special discipline in several countries. However,
in the developing world, which inhabits a large pediatric population, a limited number of neurosurgeons
manage all types of hydrocephalus across all ages. There are some essential differences in pediatric and
adult hydrocephalus. The spectrum of hydrocephalus of dysgenetic origin in a neonate and that of normal
pressure hydrocephalus of the old age has a completely different strategy of management. Endoscopic third
ventriculostomy outcomes are known to be closely associated with age at presentation and surgery. Efficacy
of alternative pathways of CSF absorption also differs according to age. Managing this disease in various
age groups is challenging because of these differences in etiopathology, tempo of the disease, modalities of
investigations and various treatment protocols as well as prognosis.
Key words:
Adult hydrocephalus, CSF shunts, neuroendoscopy, pediatric hydrocephalus

Key Message:
Hydrocephalus at various ages presents in different ways and has different causative factors. The challenges
of managing a child with large head with developmental de‑ lay, a young adult with tumoral hydrocephalus
and an elderly individual with subtle cognitive regression needs this understanding. Lifelong need of a CSF
diversion is different from a temporizing procedure while complication management requires more emphasis
in quality‑ of‑life issues. Greater awareness of these factors and proper individualization of their treatment
are emphasized by elaborating these differences.

A contemporary definition of hydrocephalus

by Rekate (2009) states that “hydrocephalus
is an active distension of the ventricular system
Etiology

The prevalence of hydrocephalus shows a

Department of
1
Neurosurgery, Bombay
Hospital Institute of
Medical Sciences,
2
B J Wadia Hospital
for Children, Mumbai,
Maharashtra, India
Corresponding Author:
Dr. Chandrashekhar
Deopujari,
114 MRC, Bombay
Hospital, New Marine
Lines, Mumbai - 400 020,
Maharashtra, India
Email:
d.chandrashekhar11@
gmail.com
of the brain related to inadequate passage of CSF
from its point of production within the ventricular
system to its point of absorption into the systemic
circulation.”[1]
Adult and pediatric hydrocephalus have been
extensively analysed separately, but to the
best of our knowledge, no paper has analysed
the differences between adult and pediatric
hydrocephalus. This narrative review aims
to address this knowledge gap and highlight
the differences between adult and pediatric
hydrocephalus concerning etiopathology,
clinical presentation, imaging modalities, and
use of other investigative methods at various
ages along with their treatment and anticipated
outcomes.
This is an open access journal, and articles are distributed under the terms
of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0
License, which allows others to remix, tweak, and build upon the work
non‑commercially, as long as appropriate credit is given and the new
creations are licensed under the identical terms.
For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com
bimodal distribution affecting pediatric age
groups and elderly population more than general
adults.[2] Age stratification helps in understanding
the basic etiology causing hydrocephalus
affecting different groups and allows us to tailor
the management based on this understanding.
With the routine prenatal ultrasound and evolution
of MRI, fetal hydrocephalus is being increasingly
diagnosed.[3] Congenital hydrocephalus may be
associated with multiple other intracranial or
extracranial anomalies.[4] X linked Hydrocephalus
due to aqueductal stenosis is known to occur
due to genetic alterations in the L1 cell adhesion
molecule (L1CAM) and may be associated with
agenesis of corpus callosum, spastic diplegia
or MASA syndrome.[5] Oi classified congenital
hydrocephalus into 3 categories [Figure 1].[6]
How to cite this article: Deopujari C, Mohanty C,
Agrawal H, Jain S, Chawla P. A comparison of Adult and
Pediatric Hydrocephalus. Neurol India 2021;69:S395-405.
Submitted: 19‑Aug‑2021 Revised: 24-Aug-2021
Accepted: 01‑Oct‑2021 Published: 11-Dec-2021

© 2021 Neurology India, Neurological Society of India | Published by Wolters Kluwer - Medknow S395
 Deopujari, et al.: Adult and pediatric hydrocephalus
Neonatal and infantile hydrocephalus may be caused due
to obstruction of CSF flow in a similar manner or presence
of structural lesions viz. arachnoid cyst or tumour, or
malformations like Dandy‑Walker and Chiari I or II. This
age group may also see communicating hydrocephalus in
a post haemorrhagic  (especially in pre‑term neonates) or
in a post infectious setting even after successful treatment
as a delayed sequela. Intrauterine infections with CMV or
Toxoplasmosis may also present as neonatal or infantile
hydrocephalus.[7]
Older children and young adults may develop hydrocephalus
secondary to meningitis during active disease or as a
delayed sequela. Tuberculous meningitis may result in
communicating or obstructive hydrocephalus  (TBMH)
in the developing world. [8,9] Presence of intraventricular
tumors like choroid plexus papilloma  (hypersecretory)
or the 4 th   ventricular tumors like medulloblastoma or
ependymoma (obstructive) are some other important causes
in this age group.[2,10]
Apart from tumours, elderly population may be afflicted with
the well‑defined entity, “Normal Pressure Hydrocephalus”,
of complex etiopathology. [10,11] [Figure 2] shows various
mechanisms at work at different stages of life.
Pathophysiology
Congenital and neonatal
The classification into “obstructive” and “communicating”
types represents an oversimplification of a rather complex
multifactorial condition.[12] Congenital hydrocephalus usually
consists of two mechanisms – primary genetic abnormalities
and secondary injuries due to altered CSF dynamics.[12] Genetic
abnormalities  (Mutations in the transmembrane protein 67
and ZCCHC8, the zinc finger CCHC‑type domain) in the cilia
and sonic hedgehog (SHH) pathway are causes of congenital
hydrocephalus.[13]
Figure 1: Classification of congenital Hydrocephalus.[6] Chart showing etiology of
fetal, neonatal and infantile hydrocephalus
Figure 2: Obstructive and Communicating Hydrocephalus at various ages. Chart
depicting common causes of hydrocephalus in different age groups
S396 Neurology India | Volume 69 | Supplement 2 | November-December 2021
Secondary injuries result from the presence of neurotrophic
factors in CSF leading to altered neurogenesis, loss of
ependymal cells which leads to exposure of neural progenitor
cells to ventricular CSF, dysfunction of the subcommissural
organ leading to aqueductal stenosis, a higher concentration
of glial fibrillary astrocytic protein in CSF leading to astrocytic
activation with subsequent glial scarring and reduction of
ventricular compliance and neuroinflammation secondary to
microglial activation.[12]
The “bulk flow theory” proposed by Cushing has come under
scanner recently. The “hydrodynamic theory” proposes that
ventricular CSF obstruction leads to ventricular dilatation,
compression of brain parenchyma, and reduction of
supratentorial subarachnoid spaces.[14] Rekate believes that all
forms of hydrocephalus are obstructive and hypersecretory
hydrocephalus is the only real communicating type and
suggested use of injected dye studies to determine the site
of obstruction.[1] Oi and di Rocco[15] have elaborated on the
“evolution theory” of CSF dynamics. They believe that
maturation of arachnoid granulations is achieved during
infancy and hence during this period minor CSF pathways e.g.,
trans‑ependymal CSF passage through the brain parenchyma,
are active. This may explain the high rates of failure of ETV in
neonates and young infants.[15,16]
Post‑infectious hydrocephalus secondary to pyogenic
meningitis in neonates is significant in two different scenarios;
1 – in full‑term neonates with difficult labour where meningitis
occurs early and may not be identified as part of general
sepsis, and 2 – in preterm neonates who develop meningitis
later with either the mother as a source or as hospital‑acquired
infection.[17] Intraventricular fibrous adhesions leading to
the formation of septations may result in multiloculated
hydrocephalus.[18] It is pertinent to note that in TBMH, the
intraventricular CSF pressures may be low and many of them
can be managed conservatively with CSF diversion restricted
to select cases.[17]
Older children and young adults
There are three main types of hydrocephalus affecting adults
and older children namely – obstructive (secondary to tumors
or cysts), communicating (post‑infective or post‑ hemorrhagic)
and hypersecretory (e.g. choroid plexus tumors).[19]
Intraventricular bleed leads to the disruption of the ependymal
surface and impaired ion and small molecule transport
between the CSF and the cerebral parenchyma and breaking
the blood‑brain barrier leading to impaired normal osmotic
gradient. [20] Another factor is inflammation leading to
arachnoid dysfunction and pulsatility and reduced CSF flow
due to fibrosis. This mechanism is unclear in adult IVH.[20]
Aquaporin‑1 is expressed at choroid plexus whereas
Aquaporin‑4 is expressed at the ependymal lining, glia
limitans and pseudopodia of astrocytes at the blood‑brain
barrier helping in movement of CSF across tissues. There is
significant alteration in AQP expression in hydrocephalus,
downregulation of AQP‑1 resulting in reduced CSF production,
and upregulation of AQP‑4 improving CSF absorption, helps
in compensating early hydrocephalus and maybe targets for
medical management.[21]
 Deopujari, et al.: Adult and pediatric hydrocephalus
Normal Pressure Hydrocephalus in the elderly
The pathophysiology of the typical symptoms in NPH has
been best described by Wang et al. recently.[22] This has been
summarised in [Figure 3]. Oi described the entity of obstructive
low‑pressure hydrocephalus (LOVA), which may manifest like
NPH in the elderly.[23]
Clinical Presentation
Neonates and Infants: They may present with refusal to feed, failure
to thrive, multiple bouts of vomiting, irritability, lethargy, bulging
tense anterior fontanelles with HC  >2.5 SD for age or crossing
two major lines on the WHO growth chart for age, sunsetting
phenomenon, unilateral or bilateral 6th nerve palsy, difficulty in
breathing (esp. in Chiari 2 Malformation) and neurogenic stridor.[24]
Decerebrate posturing may be seen as a late phenomenon.
Congenital anomalies resulting in slowly progressive
hydrocephalus may manifest with isolated increase in head
size and may warrant intervention before development of
raised ICP symptoms.[25] Head circumference measurements
are of little value after infancy.[26]
Children (after AF is fused) and young adults may present with
progressive headache, vomiting (early morning crescendo headache
followed by vomiting), and lethargy, drowsiness, progression to
stuporous or comatose state. Patients may present with transient
visual obscuration, blurring of vision, and loss of vision in chronic
cases. These patients may demonstrate papilledema initially and
if left uncorrected, may lead to optic atrophy.[24] Lastly, they may
also have decerebrate posturing as a late phenomenon.
Elderly population suffering from NPH may present with
Hakim’s triad: dementia, gait ataxia  (difficulty in initiating
gait, magnetic gait), and urinary incontinence.[27]
Imaging
Ultrasonography, CT scanning and MR imaging [Figure 6] are
the main imaging modalities for hydrocephalus. Their utility,
Figure 3: Development of NPH.[22] Flow chart depicting sequence of events leading to NPH
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S397
characteristic findings as well as limitations are summarised
in [Figure 4].[28‑45]
CSF flow studies: CSF flow studies in form of Cine PC‑MRI are
useful in diagnosis of aqueductal stenosis by demonstrating
blockage of CSF flow at the level of the aqueduct. CSF flush
peak occurs much earlier in these patients with an almost
50% reduction in atrioventricular delay.[46] Another important
application is in evaluation of patency of stoma created during
third ventriculostomy. [47] Occasionally, a few cases may
develop asymptomatic and stable ventricular enlargement
due to partial obstruction to CSF flow e.g., partial block at the
aqueduct. These cases can deteriorate due to decompensation
at any time and partial obstruction to the flow of CSF at
the aqueduct can be determined by Cine PC‑  MRI and
appropriate treatment  (shunt or ETV) can be instituted.[48]
Stroke volume (SV) which is defined as the mean volume of
CSF passing through the aqueduct during both systole and
diastole, ≥42 μL, serves as an indicator of post shunt outcomes
in patients with NPH.[49]
Functional imaging: Single‑photon emission computed
tomography (SPECT) and positron emission tomography (PET)
can show decrease of brain metabolism and cerebral blood
flow in frontobasal and anterior periventricular region.[39]
Shunt responsive patients show an improvement in the brain
glucose metabolism. But their diagnostic and prognostic values
remain unclear.[34]
Radiotracer imaging has fallen out of favour due to the lack of
spatial resolution and the need for ionising radiation. Similar
information can also be obtained with a CT ventriculography
and is a useful modality to assess the efficacy of ETV and other
endoscopic procedures such as aqueductal stenosis stenting
and arachnoid cyst fenestration.[36]
Other Investigations complementing study of hydrocephalus
ICP monitoring: Mean normal ICP lies between 7‑  and
15‑mm Hg for adults, between 3‑ and 6‑mm Hg for children
and between 1.5 and 6 mm Hg for infants.[50] Raised ICP, in
 Deopujari, et al.: Adult and pediatric hydrocephalus

Age Imaging features Limitations

1. Prenatal USG Performed at 18‑24 weeks to screen for systemic anomalies. Lack of anatomical details
At any gestational age, ventricle size of >10mm is considered as
enlargement([28]). The normal atrial diameter in 14‑38 weeks of gestation is
7.6 +/‑ 0.6mm.[29]
Mild FVM ‑10 to 12 mm, moderate FVM ‑ 13 to 15 mm, severe
FVM >15 mm. This classification has a prognostic value.[31]
Fetal MRI Better anatomical delineation in complex hydrocephalus and to look for Cost
additional abnormalities[29,30]). Limited availability
Influences decision making in about 25% of patients with hydrocephalus[31]
Obstructive fetal hydrocephalus  rounded configuration of the ventricles,
effacement of pericerebral subarachnoid space, disruption of septum
pellucidum, and preserved layering of the cerebral mantle in contrast to
destructive ventriculomegaly.[32]
Partial dehiscence of the mantle  severe fetal hydrocephalus. [32]
2. Newborn, infants USG Good, inexpensive, bedside screening tool through open fontanelle Posterior fossa visualization
young children Imaging follow‑up of infants with known ventriculomegaly is limited.
MRI Gold standard to visualize the ventricular system and associated Cost, limited availability,
anomalies[33]) difficult to obtain an optimal
Sagittal steady‑state T2 imaging is helpful to evaluate the suitability of ETV & study in children who are
the functioning of the ventriculostomy. irritable
Phase‑contrast sequences  CSF flow velocity and the direction of flow.[32]
DTI  microstructural changes in the white matter.
ASL perfusion imaging  measure CBF without contrast or
radio‑isotopes.[34] shows a quantified map of rCBF.Shows decreased global
perfusion which improves following shunt.[35] (still under investigation for
application)
CT Fast, efficient way to determine the size of ventricles, hence useful in Inferior anatomical details
emergency settings. & ionizing exposure (every
More widely available than MRI exposure of CT head to 97
CT ventriculography à assess the efficacy of ETV and other endoscopic children leads to a risk of
procedures such as aqueductal stenosis stenting and arachnoid cyst 1 fatal malignancy in the
fenestration.[36] lifetime.)[37]
3. Adults MRI Modality of choice to evaluate adults with hydrocephalus.
MRI with contrast  tumours are well visualized.
Presence of septae, membranes, or cysts (arachnoid cysts, neurocysticercal
cysts, pineal cysts, etc) can be visualized with steady‑state T2 imaging.[19]
Blood and remote blood products can be identified on T2
sequence. FLAIR, DWI and post‑contrast MRI helps in identification of
associated meningitis.
CT Good screening tool, Assess ventricle size in known cases of hydrocephalus
4. Elderly CT & MRI International imaging guidelines for diagnosis of NPH ([38,39])
Evans’s index >0.3
Lack of macroscopic CSF obstruction. 3.One of the following supporting
features:
Temporal horn enlargement not entirely due to hippocampus atrophy.
Callosal angle of >40°
CT and MRI ‑ Periventricular signal changes due to altered brain water
content and not entirely attributable to microvascular ischemic changes or
demyelination
Flow void on the MRI in the fourth ventricle or aqueduct of Sylvius.
Japanese NPH guidelines exclude the periventricular signal changes but
include the following additional criteria[40]
Enlarged Sylvian fissures and basal cisterns;
Narrowing of the sulci and subarachnoid spaces
Advanced DTI, fMRI have also been studied in NPH to detect biomarkers for NPH[41,42] Not widely used. Still under
MRI Regression model volumetric MRI to assess gray matter and white matter investigation
sequences has also shown high accuracy in the diagnosis of NPH.[43]
ASL perfusion imaging  Can be used before and after the LP drainage of
CSF.[35,44] & beneficial effect of acetazolamide therapy in NPH [45]

Figure 4: imaging characteristics through various ages

S398 Neurology India | Volume 69 | Supplement 2 | November-December 2021
 Deopujari, et al.: Adult and pediatric hydrocephalus
Modality Features
ICP Monitoring Normal mean:[50]
Adults: 7‑15 mmHg
Children: 3‑6 mmHg
Infants: 1.5‑5 mmHg
ICP >20mmHg for >5 mins is considered abnormal. (>15 in
children)[51,52]
SPECT Cerebral Blood Flow (CBF) based studies like with SPECT
Tc99M shows reduced relative CBF in corpus callosum and
sylvian fissure [61], with relatively increased perfusion in frontal,
parietal and occipital areas.
111In‑DTPA cisternography with SPECT/CT can help diagnose
NPH as tracer flow won’t be demonstrated over the convexity.[63]
PET 18‑FDG‑PET‑CT can also be used in diagnosis of
idiopathic‑NPH.[39]
USG: Optic Nerve Can be measures with USG as well as MRI/Thin‑CT.
Sheath Diameter Adults: 5mm
(ONSD) Children over 1 yr.: 4.5mm Infants: 4mm[64]
Figure 5: Other investigations in Hydrocephalus
an acute setting, may be considered when ICP >20mm Hg
for at least 5 min.[51,52] ICP studies may help in understanding
shunt failure in both paediatrics and adults [53] and in
differentiating active vs. arrested hydrocephalus. This helps
in preventing unnecessary shunting or shunt revision. In
children with suspected shunt malfunction, exaggerated
increase in ICP in night indicates better prognosis with
shunt revision.[54]
Indicators of shunt malfunction or active hydrocephalus were
reported in children with rise in ICP of 5 mm Hg over baseline
or the shunt working pressure, increased peak ICP levels above
25 mm Hg during REM sleep and increase of RAP index above
0.6 at baseline or during REM sleep.[55]
Additionally, in cases with chronic ventricular dilatation ICP
may not be raised greatly. Any obstruction to absorption of
CSF may be evaluated via CSF infusion tests through lumbar
puncture or a ventricular access device. Baseline ICP and
Rcsf (increase in ICP during infusion ÷ infusion rate) values
are calculated. Rcsf values below 13 mm  Hg/(ml/min) are
considered normal while values above 18 mm  Hg indicate
disturbance in CSF flow.[56] The resistance to CSF outflow
increases with age in both normal individuals and also in
patients with NPH and adjusted Rcsf values for age should
be considered while interpreting the results.[57]
Cerebral Blood Flow Studies: Chronic hydrocephalus with
or without raised ICP may be associated with global reduction
in CBF and alteration in cerebral autoregulation. [58,59]
Reduction in CBF is secondary to raised CSF pressures
leading to cortical compression and neuronal stretching.
Effects of reduced CBF including ischemic changes may
be reversible following VP shunt surgery.[60] Regional CBF
is also reduced in certain areas like the thalamus and the
basal ganglia regions while it may be normal in the white
matter regions.[61] Regional blood flow alteration measured
using PET is important in assessment of NPH and post
VP shunt functional changes.[62] The other investigations
complementing study of hydrocephalus are summarized
in [Figure 5].[50‑52,54,55,61‑65]
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S399
Comments
Schumann et al. [54, 55] classification (based on ICP
and rCSF) can help prevent unnecessary shunting.
Chronic hydrocephalus and NPH or IIH can be missed if
only relied upon.
SPECT is especially useful in idiopathic‑ NPH in adult
and geriatric population. Although radioisotope can be
used in children its role is limited.
Functionality of the VP shunt or arrested hydrocephalus
can also be diagnosed with tracer studies.[34]
Post VP shunt it was found that on average 1‑2.5mm of
reduction in ONSD. [65]
Management
The definitive hydrocephalus management are limited
to endoscopic third ventriculostomy  (ETV) and
ventriculoperitoneal (VP) shunts. Their application needs to
be individualized.[66] The use of temporary measures viz, EVD,
Ommaya reservoir insertion and tapping, or lumbar drainage
may also differ as per the age and clinical setting.[66] Since its
inception, shunting has probably saved more lives than any
other neurosurgical procedure, despite the high shunt failure
and malfunction rates. Despite advances in shunt technology,
the incidence of shunt failure is as high as 30% in the first year,
40% by the second year, almost 85% by 10 years, with most
studies quoting 81% by 12 years.[67,68]
Temporising measures: Medical management may be tried
to tide over the period of investigations and occasionally
to avoid an acute crisis. Most used agent is Acetazolamide.
Acetazolamide is the only approved agent for use in
hydrocephalus even though its efficacy is only at 25‑30%.[69]
It has been postulated that Acetazolamide acts by reversible
inhibition of AQP‑4 in choroid plexus and by modulation of
AQP‑1 to reduce CSF formation at the apical membrane of the
CP.[69] In addition, one may use osmotic diuretics viz. Mannitol,
oral glycerol, and 3% NaCl or Frusemide in acute setting till a
definitive procedure can be planned and executed.[70]
Neonates and infants with open anterior fontanelle can
undergo ventricular tapping as and when required to manage
over an acute event and obtain CSF for analysis. In neonates
and infants, if ventricular tapping frequency is >1 per week,
a ventricular access device may be placed  (institutional
practice) and as soon as the CSF clears, definitive shunting
may be performed. Alternative temporizing measures includes
ventriculo‑Subgaleal shunt especially in posthemorrhagic or
infectious cases that obviates need of repeated tapping.[71]
CSF Diversion procedures
The ETV success score is a vital tool in determining the
relative success of performing ETV, which is also based on
the patient’s age as an important criterion apart from other
 Deopujari, et al.: Adult and pediatric hydrocephalus

Figure 6: (a) Fetal MRI showing hydrocephalus (A – Axial, B and C – Sagittal, C – Coronal). Fetal MRI images of a case of hydrocephalus. (b) USG Skull of an infant
showing hydrocephalus. Ultrasound images via open AF in a case of infantile hydrocephalus. (c) MRI Brain (axial, T1 C+ images). MRI Brain T1WI with gadolinium showing
hydrocephalus in a case of pineal region tumor with seedings. (d) CT Brain images (axial views) in a teenager. CT Brain images in a teenager with TBMH. (e) CT Brain
images (axial views) in a young woman. CT Brain in a young woman showing subarachnoid hemorrhage along with hydrocephalus. (f) MRI of a patient with NPH of an elderly
gentleman. T2WI imaging of the brain showing classical features of NPH

factors viz. etiology of hydrocephalus and history of prior
shunt or shunt revision.[72] ETV is not advised in children, aged
less than 6 months, due to incomplete maturation of the basal
subarachnoid cisterns and the arachnoid granulations (major
CSF pathway) that absorb CSF into the venous system.[15].
Ogiwara and Tomita have shown that ETV may be performed
with favourable results ‑ 50% success rate between 3‑6 months
of age for pure aqueductal stenosis.[73]
ETV in neonates is being increasingly reported. Elbabaa
et al., have achieved 46% success rate by performing ETV
in children born with hydrocephalus who have previously
undergone antenatal MMC repair.[74] According to Schroeder
et al., neuroendoscopic aqueductoplasty is viable alternative
to ETV, especially for short segment aqueductal stenosis.[75]
It is postulated that both etiology and age of manifestation
of hydrocephalus rather than age at which ETV was done are
important for success of ETV.[76, 77]
ETV is an option in cases with posterior fossa tumour causing
obstructive hydrocephalus at all ages. In most of the cases
relief from obstruction helps in re‑establishing the CSF
pathways, however, in few cases the adaptation time may
be as long as 2‑4  months.[78] Only 6% of the patients who
underwent ETV before tumour resection needed re‑surgery for
hydrocephalus as compared to almost 27% who were managed
conservatively.[78] ETV avoided post‑shunt complications of
reverse or upward herniation and potential for intratumoral
haemorrhage due to acute change in CSF dynamics.[78]
Gangemi et al  (2008) published their paper advocating ETV
for NPH with over 50% success rate.[79] The utility of ETV for
NPH in carefully selected patients who had shorter history
or duration of symptoms, better neurological profile, and
onset with gait disturbances has been shown. They found that
sudden reappearance of normal CSF pulsations following ETV
correlated well with a good outcome.[79] Unsuspected cases
with LOVA may be the best candidates for ETV in elderly.[23]
VP shunt remains the mainstay of treatment of hydrocephalus.
Age is an important determinant to the success or failure of
shunt, and age of patient at time of implantation plays a pivotal
role in the same. Age less than 6 months carries a higher risk
of shunt failure and higher shunt revision rates.[80] One of the
major determinants in shunt selection is the opening pressure
of the shunt valve selected. An open AF warrants use of
low‑pressure shunt system.[81] Children and adults generally
require a medium‑pressure shunt system. Using shunts in
children with posterior fossa tumors and hydrocephalus is an
accepted practice.

S400 Neurology India | Volume 69 | Supplement 2 | November-December 2021

 Deopujari, et al.: Adult and pediatric hydrocephalus

However, sudden release of CSF pressures can lead to management of hydrocephalus. It was found that 40% of the
untoward complications like intratumoral haemorrhage and/ children with pre‑natal MMC repair underwent shunting as
or upward herniation.[82] compared to 82% in the post‑natal group at 1 year of age.[89]

Shunt Malfunction: The UK shunt registry study showed that
the incidence of 1‑year shunt revision rates in infants is 1.8 times
higher than adults and in children 1.4  times higher than
adults.[83] The same paper also showed that the most common
reason of shunt surgery was perinatal IVH, tumours and
NPH in infants, children (and adults) and elderly (>65 years)
respectively. Underdrainage of CSF was the most common
cause of shunt revision across all age groups. Shunt infection
rates were highest in neonates, compared to other age groups.[84]
CSF over drainage leading to formation of subdural hematoma
is seen in patients with NPH with incidence of about 10%.[85,86]
Subdural hygromas secondary to CSF over drainage is also
seen in infants and young children more commonly than
adults.[86,87] Chronic CSF over drainage can also lead to slit
ventricle syndrome, which is more commonly seen in older
children and young adults compared to other age groups.[86]
Different shunt valve systems are available. Broadly they can be
classified in differential pressure valves (DPV) or flow regulated
valves (FRV). DPV are used commonly in practice. They may be
fixed DPV or adjustable (programmable) valves. A low‑pressure
shunt system may result in over drainage with subsequent
subdural hematoma formation. Such cases may benefit from
a programmable valve, the opening pressure of which can be
manipulated non‑ invasively by using a programmer. Care has to
be taken to avoid exposure of the valve to strong magnetic fields.
NPH patients preferably should be shunted with programmable
valve It has been suggested to use a programmable valve with
the highest setting and then, depending on the response of
the patient, to gradually reduce the pressure by 30 mm H2O
gradations until adequate response is obtained.[88]
Avoiding Hydrocephalus
The MOMs trial and its success has given one more avenue
to the neurosurgeon and the only preventable option for
Prof. Samii has described a novel technique of preventing a VP
shunt in secondary acute hydrocephalus by gradual weaning
off of the implanted EVD and systematically raising the CSF
pressure so that the normal production‑absorption balance is
achieved obviating the need for permanent CSF diversion.[90]
A gradual discontinuation of EVD in aneurysmal SAH helped
several patients in preventing VP shunt procedure in a
Scandinavian multi‑ institutional survey.[91]
Management of hydrocephalus in different age groups have
been summarised in [Figure 7].
Outcome Parameters and Prognosis
1. Prenatal: The natural history of fetal ventriculomegaly (FVM)
is variable. Many of the cases of FVM stabilises as the
pregnancy progresses  (57%), while in 29% of the cases
spontaneous resolution can be seen. [92,93] Progression
of FVM is seen in only 14% of the cases. [91] Another
importance of parent counselling involves the awareness
of a risk of recurrence of FVM in future pregnancies.
Therefore, identification of the etiology of the FVM is
critical. Most of the parents are counselled for detailed
ultrasonography at 18  weeks to rule out FVM in future
pregnancies. In case of a prior genetic abnormality,
amniocentesis is recommended in future pregnancies.
[92,93,94]
The risk of FVM in future pregnancies in cases of
FVM without an identifiable etiology is less than 4%.[95]
The survival rate of mild FVM is about 98%, moderate
FVM is 80% and severe FVM is only 30%.[96] Neurological
outcome studies show only 8% of mild and moderate FVM
cases had a developmental delay compared to only 8%
of children having normal neurological outcome in cases
of severe FVM.[92,93,96-99] Poor neurological outcome is also
closely associated with progression of ventriculomegaly
in the prenatal period.[92,93]

Figure 7: Flow chart depicting management of hydrocephalus across various ages. (CPP = choroid plexus papilloma, CSF = cerebrospinal fluid, ETV = endoscopic third
ventriculostomy, EVD = external ventricular drain, HCP = hydrocephalus, IVH = intraventricular hemorrhage, LOVA = long standing overt ventriculomegaly in adults,
NPH = normal pressure hydrocephalus, Rx = treatment, VP = ventriculoperitoneal)

Neurology India | Volume 69 | Supplement 2 | November-December 2021 S401

 Deopujari, et al.: Adult and pediatric hydrocephalus

Neonatal & Infantile Older children & young Elderly

adults
Etiology Congenital, X-linked, Neonatal Aqueductal stenosis, Tumors, NPH and rarely post-
hemorrhage, Aqueduct stenosis and other post-infectious, tumors infective/post-hemorrhagic
anomalies, Infection & Tumors rare (obstructive, secretory)
Clinical Presentation Rapid increase in ICP, increasing head
size, downgazing, vomiting,
Developmental delay headache, vomiting, raised ICP in tumors & Clinical syndrome of
learning disability in slow developing hcp NPH
Imaging USG skull (till fontanelles open), MRI CT/MRI Advanced MRI techniques with CSF
flow & rCBF measurements
Treatment Long term view & Individualised, ETV only ETV/VP shunt as per Programmable VP shunt primarily for
> 6 months age pathology NPH, occasional ETV
Outcomes Based on primary pathology. Equipoise for Lower revision rates for Lower revision rates for
ETV and shunt, Higher revision rates VP shunt as well as ETV programmable VP shunt in NPH,
high risk of SDH
Figure depicting the essential differences in etiology, presentation, and management of hydrocephalus across various age groups.

Figure 8 : Essential differences between in hydrocephalus at various age groups

2. Newborns, infants, and children: The outcome is dependent
not only on the etiology of the hydrocephalus but also
on the brain insult by the inciting cause (e.g. – infection,
hemorrhage).[66] Thus, it is not surprising that in the children
with aqueductal stenosis without any other structural brain
anomalies will have normal to near‑normal neurological
outcomes.[66]
About 30‑48% of children have accompanying
epilepsy.[100] Quality of life outcomes in children with
epilepsy is consistently worse than in children without
epilepsy.[100] In addition, shunt‑related complications due
to shunt revision, shunt infection, duration of hospital stay
are some of the other factors associated with poor QoL.[100]
A study of children with infantile hydrocephalus revealed
delayed cognitive development in 36% of cases.[101]
3. Young adults: This group has not been studied as
extensively as the other age groups. Comparison to
normal control adults, adults with hydrocephalus  (due
to aqueductal stenosis or post meningitic hydrocephalus)
had poorer performance on reading, attention, motor
coordination, frontal lobe functions, and visual, semantic,
and working memory. This impairment was not related to
etiology, age, sex, or shunt position. This has been attributed
to the damage of the fornix due to dilation of the third
ventricle.[102]
4. Elderly: The outcomes of NPH are distinct from other causes
of hydrocephalus. Most of the patients deteriorate without
CSF diversion procedure as early as 3  months.[103] Hebb
et al. in their metanalysis noted that the mean complication
rate of shunt surgery was about 38%, while the need for
additional surgery was 22% with the risk of a permanent
neurological deficit or death at 6%.[104] However, a more
recent systematic review showed a more positive outlook
with shunt surgery resulting in 82% improvement with a
low mortality rate of 0.2%, and a lower complications rate
of 8.2%.[103] Shunting had a very favourable outcome on
gait and less improvement in cognition.[105] The absence of
cardiovascular risk factors, younger age, and absence of
white matter lesions on MRI was associated with a good
gait outcome following shunt surgery.[105] Interestingly,
Though ETV for LOVA may be the right procedure and
may have accounted for the success in Gangemi series, ETV
for NPH resulted in a higher mortality with a higher short
term complication rate compared to a shunt in a recent
study.[106]
Conclusion
There are distinct differences in the etiology, presentation,
modes of investigation, and management of hydrocephalus in
pediatric and adult populations [summarised in Figure 8]. This
can be further subdivided into neonates, infants, older children,
young adults, and late age periods for better understanding of
the disease process and expected outcomes. Age stratification
along with knowledge of etiopathogenesis of the disease helps
in tailoring the treatment to the individual patient.
Abbreviations: AF = Anterior Fontanelle, AQP = Aquaporin,
CMV  =  Cytomegalovirus, CSF  =  Cerebrospinal Fluid,
CT  =  Computed Tomography, HC  =  Head Circumference,
ICP = Intracranial Pressure, IVH = Intraventricular Hemorrhage,
LOVA  =  Long‑Standing Overt Ventriculomegaly in Adults
MRI  =  Magnetic Resonance Imaging, MASA  =  Mental
Retardation, Aphasia, Shuffling Gait, Adducted Thumbs,
NPH = Normal Pressure Hydrocephalus, PC = Phase Contrast,
QoL  =  Quality of Life, RAP  =  the correlation coefficient  [R]
between AMP amplitude  [A] and mean pressure  [P] the
correlation coefficient  [R] between AMP amplitude  [A]
and mean pressure  [P], REM  =  Rapid Eye Movement,
SAH = Subarachnoid Hemorrhage, SD = Standard Deviation,
TBMH  =  Tuberculous Meningitis With Hydrocephalus,
VP = Ventriculoperitoneal, WHO = World Health Organization.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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95. Váradi V, Tóth Z, Török O, Papp Z. Heterogeneity and recurrence
risk for congenital hydrocephalus (ventriculomegaly): a prospective
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96. Gaglioti P, Oberto M, Todros T. The significance of fetal
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97. Pagani G, Thilaganathan B, Prefumo F. Neurodevelopmental
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98. Breeze, Andrew CG, et al. Obstetric and neonatal outcomes in
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101. Fernell E, Hagberg G, Hagberg B. Infantile hydrocephalus
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102. Donnet A, Schmitt A, Dufour H, et al. Differential patterns of
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103. Toma AK, Papadopoulos MC, Stapleton S, Kitchen ND,
Watkins LD. Systematic review of the outcome of shunt surgery in
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104. Hebb AO, Cusimano MD. Idiopathic normal pressure hydrocephalus: a
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placement for idiopathic normal‑ pressure hydrocephalus: a
population‑based study. Neurosurg 2013;73:951‑60.
 Review Article

Access this article online

Quick Response Code:
Normal‑Pressure
Hydrocephalus ‑ Patient Evaluation
and Decision‑Making
Deepti Vibha, Manjari Tripathi
Website:
www.neurologyindia.com

DOI: Abstract
10.4103/0028-3886.332267
Background: Normal‑pressure hydrocephalus  (NPH) presents with the triad of gait difficulty, urinary
incontinence, and cognitive decline. However, the definitive diagnosis and treatment may be challenging at
times due to secondary causes of NPH (sNPH) versus idiopathic NPH (iNPH), co‑existing other degenerative,
vascular, and metabolic causes of similar clinical presentations.
Objective: The objective of this narrative review is to outline the approach to patient evaluation and
decision‑making in cases where there is clinical suspicion of iNPH.
Methods: This review article intends to provide a practical approach to the patients with a suspected diagnosis
of iNPH.
Results: The cardinal clinical features with a guide from investigations like magnetic resonance imaging (MRI)
brain and cerebrospinal fluid (CSF) analysis, and CSF tap assessment have been outlined. The interpretation
of conflicting MRI brain findings or CSF analysis may need resolution by further tests. The decision algorithm
following the examination and investigations has been included to address the dilemma in the case of a
non‑supportive MRI and/or CSF tap test.
Conclusion: iNPH is a treatable cause of the cognitive decline and gait disorder. While neurodegenerative causes
may accompany iNPH, any patient with improvement after CSF drainage deserves therapeutic intervention.
Key Words:
Cerebrospinal fluid, diagnosis, lumbar puncture, normal‑pressure hydrocephalus

Key message:
iNPH is a treatable cause of gait disturbance with cognitive decline. While it may coexist with other
neurodegenerative disorders, 80% patients may benefit from treatment in probable iNPH.

I n 1965, Hakim and Adams published a case

series of three patients with ‘normal‑pressure
hydrocephalus (NPH)’ who improved
dramatically with neurosurgical shunting
procedures.[1] The cardinal symptoms of NPH
are gait impairment, urinary incontinence, and
dementia. The imaging studies of the brain reveal
ventriculomegaly without any marked degree
Department of of cortical atrophy. Later, primary (idiopathic)
Neurology, All India normal‑pressure hydrocephalus (iNPH) was
Institute of Medical demarcated from secondary normal‑pressure
Sciences, New Delhi, hydrocephalus (sNPH), which was caused by
India subarachnoid hemorrhage (23%), meningitis (4.5%),
or traumatic brain injury (12.5%).[2]
Address for
correspondence:
Prof. Manjari Tripathi,
The prevalence of iNPH has been estimated
Professor, Department of to be 0.2% in the age group of 70–79 years,
Neurology, Room Number and 5.9% for 80 years and older, in a Swedish
705, Neurosciences
Center, All India Institute This is an open access journal, and articles are distributed under the terms
of Medical Sciences, of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0
New Delhi ‑ 110 029, License, which allows others to remix, tweak, and build upon the work
India. non‑commercially, as long as appropriate credit is given and the new
creations are licensed under the identical terms.
E‑mail: Manjari.tripathi@
gmail.com For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com
population‑based study. [3] While the exact
mechanism for iNPH is still open to discussion,
it is speculated to be multifactorial, due to the
interplay of disturbed cerebrospinal fluid (CSF)
dynamics and compromised brain function.
The disturbances in the CSF dynamic system
contribute to ventricular enlargement and the
dysfunction of the brain parenchyma leading to
impaired CSF outflow resistance and increased
intracranial pressure pulsatility. This leads to
reduced subcortical blood flow and ischemia in
the periventricular areas.[4] This is also reflected
in the magnetic resonance imaging (MRI) brain
changes which will be discussed subsequently.
This review is restricted to the patient evaluation
and decision‑making about the management in
a suspected case of iNPH.
How to cite this article: Vibha D, Tripathi M.
Normal-Pressure Hydrocephalus - Patient Evaluation
and Decision-Making. Neurol India 2021;69:S406-12.
Submitted: 27-Jun-2021   Revised: 27-Aug-2021
Accepted: 13-Sep-2021   Published: 11-Dec-2021

S406 © 2021 Neurology India, Neurological Society of India | Published by Wolters Kluwer - Medknow
 Vibha and Tripathi: Evaluation NPH
Patient Evaluation
The diagnosis of iNPH is made by a combination of clinical
history, physical examination, CSF tap test, and brain imaging.
The clinical history is characterized by chronic onset and
insidiously progressive disorder involving walking difficulty
and/or balance problems with impairment in control of
urination and cognitive decline, usually in that order.
However, the complete triad of gait, bladder and cognitive
disturbances may be present in only 50–75% of the patients.[5]
Clinical features:
Gait disturbances:
The gait pattern in iNPH has been classically described as
a magnetic gait or gait apraxia. However, small‑stepped
parkinsonian gait, as well as ataxic broad‑based gait, has also
been described.[6,7] The triad of decreased stride length, decreased
foot‑to‑floor clearance, and a broad‑based gait have been
described in NPH. The stride length improves most distinctly
following a diagnostic spinal tap. A quantitative assessment of
the gait remains an important parameter for the confirmation of
diagnosis as well as therapeutic response. The gait domain in the
iNPH scale[8] is evaluated by the means of the measurements of
the number of steps and seconds needed to walk 10 m at a free
pace, and an ordinal rating of the gait is then done. There are
automated gait analyzer machines which have been used in recent
studies,[9] although studies and guidelines mention the following
ordinal scale[8]: 1 Normal. 2 Slight disturbance of tandem walk and
turning. 3 Wide‑based gait with sway, without foot corrections.
4 Tendency to fall, with foot corrections. 5 Walking with a cane.
6 Bi‑manual support is needed. 7 Aided. 8 Wheelchair bound.
For bedside clinical evaluation, the parameters mentioned
in Table 1[11] may help in the screening. For patients who are
non‑ambulatory, upper‑extremity coordination and speed tasks
like line tracing and serial dotting tests may be used.[10]
Cognitive impairment:
Psychomotor speed, attention, and working memory are most
frequently impaired in iNPH. Although the cognitive decline
may be the last clinical feature in the chronology of symptoms,
it may be picked up earlier via suitable tests. In the late stage
apathy, reduced drive, indifference, bradyphrenia, reduced
speech production, and rarely, akinetic mutism may occur.
This may be mistaken by the caregivers to be due to depression
and lead to delay in the treatment. The clinical assessment of
the cognitive decline is done via the grooved pegboard test,
the Stroop test, and the Rey auditory‑verbal learning test in
the iNPH grading.[8] However, simpler tests for frontal lobe
function assessment like the digit span test and trail‑making
A/B test may also be used for out‑patient assessment. Early
CSF shunting can still improve the cognitive deficits in as
Table 1: Gait characteristics in iNPH
Gait characteristics Abnormal findings
10 meter gait test >13 steps, taking >10 s
Step breadth Distance between toes >1 ft length
Step length <1‑foot distance between the heel of the
front foot and the toe of the rear foot
360° turn >4 steps
Foot placement Foot position correction >25% of steps
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S407
many as 80% of the patients with iNPH.[12] Therefore, it is a
crucial part of the assessment in any elderly with predominant
symmetric gait disturbance. It has been shown that Alzheimer’s
and vascular pathology can coexist with iNPH and make the
definitive diagnosis challenging.[13]
Urinary bladder dysfunction:
The disturbances of the bladder function in iNPH result from
detrusor hyperactivity due to a progressive degree of central
inhibitory control. The iNPH grading is as follows: 1 Normal.
2 Urgency without incontinence. 3 Infrequent incontinence
without a napkin. 4 Frequent incontinence with a napkin.
5 Bladder incontinence. 6 Bladder and bowel incontinence.
It is important that the history of urinary symptoms be
confirmed by a reliable caregiver since the associated cognitive
and behavior disturbance can make the patient’s version
unreliable. CSF shunting can improve bladder dysfunction in
as many as 80% of the iNPH patients if performed early, but
in no more than 50–60% if performed in an advanced stage
of the disease.
Brain imaging:
Neuroimaging, at least Computerized Tomography (CT) head
or preferably MRI is required for the diagnosis of iNPH.
The cardinal features to be fulfilled are the presence of
hydrocephalus without any evidence of obstruction or marked
cerebral atrophy. The simplest screening test for ventricular
enlargement is the Evans index, which is the ratio of the widest
frontal horn span to the widest diameter of the brain on the
same axial image [Figure 1]. An Evans ratio of more than 0.3
indicates ventriculomegaly.
However, ventriculomegaly can be secondary to the loss of
cerebral matter, as in degenerative dementias. To differentiate
hydrocephalus ex vacuo, from iNPH, the Sylvian fissures need
to be examined in the MRI brain. If they are widened out of
proportion to the cortical sulci, which are flattened (‘‘high tight’’
convexity), it favors iNPH. The Japanese researchers have
described this as disproportionately enlarged subarachnoid
space hydrocephalus (DESH).[12] It should be noted that rarely
“asymptomatic ventriculomegaly with features of iNPH on
MRI (AVIM)” may also exist. The clinical significance, however,
is less known.
Figure 1: Evan's Index
 Vibha and Tripathi: Evaluation NPH

Almost all patients with iNPH also have periventricular
white matter lesions that are best seen in the fluid‑attenuated
inversion recovery  (FLAIR) or T2 sequences. These are
considered to reflect the fluid movement from the ventricles
into the parenchyma. The additional MRI features for the
diagnosis of iNPH are[2] the enlargement of the temporal horns
of the lateral ventricles not entirely attributable to hippocampus
atrophy, callosal angle of 40° or more, and an aqueductal or
fourth ventricular flow void on MRI.
Another investigated imaging modality is the phase‑contrast
MRI sequence done at the level of the aqueduct to determine
the ‘aqueductal CSF stroke volume  (ACSV)’.[14] It has been
observed that the patients who respond to shunting for iNPH
have at least twice the ACSV of healthy elderly patients. While
there is no standard cut‑off value for velocities, if there is a
significant decrease in the ACSV in the pre‑  and post‑CSF
tap values, it may also suggest a good response with the
Ventriculo-peritoneal (VP) shunt.[15,16] Various studies have
taken elevated aqueductal CSF flow as  >18  mL/min[17] to
24 mL/min,[18] while other studies have emphasized the
difference in the pre‑ and post‑tap velocities. [15] Hence,
standalone MRI features and dynamic changes in conjunction
with the CSF tap test may help in making the decision for
further CSF diversion procedures.
CSF tap test and external lumbar drainage:
Once the clinical possibility of iNPH is made via the clinical and
neuroimaging tests, the CSF tap test is the next logical step. It
requires the removal of CSF (30–50 mL) which is carried out via
a lumbar tap. A tap test is less invasive to the external lumbar
drain which involves the removal of a large volume of CSF (300–
500 mL). The compilations such as disconnection or fracture
of the indwelling catheter, radicular pain, or meningitis were
reported in 2–8% of the patients with external lumbar drain. The
tap test has a sensitivity of 28–62% and a specificity of 33–100%.
The interval between the Lumbo-peritoneal (LP) and the formal
follow‑up examination is usually between 2 and 4 h. A repeat
assessment is usually carried out at 24 and 72 h,[19] although the
symptoms may keep improving up to a week.[6] A positive test
is considered if there is ≥10% improvement on the Timed Up
and Go test (TUG), ≥ 3‑point improvement on the Mini‑Mental
State Examination (MMSE), or ≥ 1‑point improvement in any
component of the classical symptom triad as used in the iNPH.[20]
In the event of strong clinical suspicion, but no improvement
on tap test, the tap test may be repeated with a broader gauge

Table 2: Diagnosis of iNPH (adapted from[2])

Probable iNPH
History Insidious onset (vs. acute)
Origin after age 40 years
A minimum duration: at least 3‑6 months
No evidence of an antecedent event such as head trauma,
intracerebral hemorrhage, meningitis, or other known causes
of secondary hydrocephalus
Progression over time
No other neurological, psychiatric, or medical conditions can
explain the presenting symptoms
Clinical Gait/balance disturbance must be present, plus at least one
other area of impairment in cognition, urinary symptoms, or
both
Brain imaging: A brain Ventricular enlargement not entirely attributable to cerebral
imaging study (CT or atrophy or congenital enlargement (Evan’s index >0.3 or
MRI) performed after comparable measure)
the onset of symptoms No macroscopic obstruction to CSF flow
At least one of the following supportive features:
Enlargement of the temporal horns of the lateral ventricles
not entirely attributable to hippocampus atrophy
Callosal angle of 40° or more
Evidence of altered brain water content, including
periventricular signal changes on CT and MRI not attributable
to microvascular ischemic changes or demyelination
An aqueductal or fourth ventricular flow void on MRI
Physiological CSF opening pressure in the range of 5‑18 mmHg (or
70‑245 mm H2O) as determined by a lumbar puncture or a
comparable procedure
Unlikely iNPH
No evidence of ventriculomegaly
Signs of increased intracranial pressure such as papilledema
No component of the clinical triad of iNPH is present.
Symptoms explained by other causes (e.g., spinal stenosis)
Possible iNPH
Subacute or indeterminate mode of onset
Any age after childhood
Less than 3 months/indeterminate
May follow events such as mild head trauma, remote
history of intracerebral hemorrhage, or childhood and
adolescent meningitis or other conditions that may not
be causally related.
Nonprogressive or not clearly progressive
Coexisting with other neurological, psychiatric, or
medical disorders but in the judgment of the clinician is
not entirely attributable to these conditions
Symptoms of either
Incontinence and/or cognitive impairment in the
absence of an observable gait or balance disturbance
Gait disturbance or dementia alone
Ventricular enlargement consistent with hydrocephalus
but associated with any of the following:
Evidence of cerebral atrophy of sufficient severity to
potentially explain the ventricular size.
Structural lesions that may influence the ventricular
size
Opening pressure measurement not available or
pressure outside the range required for probable iNPH

S408 Neurology India | Volume 69 | Supplement 2 | November-December 2021

 Vibha and Tripathi: Evaluation NPH
needle, indirect assessments in the form of CSF flow studies, or
an external lumbar drain may be considered. The large volume
removal of CSF (300–500 mL) is carried out via an external lumbar
drain. The external lumbar drain is kept over several days and
clinical assessments are repeated. The complications such as
disconnection or fracture of the indwelling catheter, radicular
pain, or meningitis can occur in 2–8% of the patients. While the
tap test has a sensitivity of 28–62% and specificity of 33–100%, the
external lumbar drain has a sensitivity of 60–100% and a specificity
was 80–100%.[12] Other invasive tests like intracerebral pressure
monitoring[21,22] and CSF dynamics test (CSF space volume load
test)[22] can be done depending upon the expertise of the centers.
Other investigations like the positron emission
tomography (PET) may help in the exclusion of associated
alternative or associated degenerative dementias.[23‑25]
The purpose of the battery of clinical examination and
investigations is to categorize patients into possible, probable
iNPH[2] [Table 2] to provide more evidence for the evaluation
of alternative diagnosis or definitive therapy. While the
International[2] and Japanese[12] guidelines are conceptually
similar, they have different age cut‑offs and emphasis on
clinical features. [26] The diagnostic guidelines have also
provided a checklist of gait, cognition, bladder disturbances,
and radiological parameters which are useful in both clinical
and research settings [Table 3].
• Other infrequently done tests:
The measurement of the cerebral blood flow  (CBF) in
iNPH can be done by single‑photon emission computed
tomography  (SPECT) utilizing radio‑labeled materials.
Studies have variously described hypoperfusion around the
corpus callosum, Sylvian fissures, frontal lobe, and other
areas.[27‑30] However, due to the lack of association of the
CBF measurements in predicting shunt responsiveness, this
modality is not used much currently.
Radioisotope  (RI) or CT cisternography has also been used
earlier for the diagnosis of NPH, which has findings of
intraventricular reflux and stagnation of the isotope and contrast
medium on the brain surface.[31,32] Due to the invasiveness and
low diagnostic accuracy of CT or RI cisternography, it is
currently not necessary for the diagnosis of iNPH. It may be
done in specialized centers for identifying obstructions in the
circulation of CSF. The practice guidelines from the American
Academy of Neurology have provided Class IV evidence for
this test for predicting response to shunt.[33]
Differential Diagnosis
The differential diagnosis of iNPH is exhaustive, and the
differential diagnoses may coexist with iNPH and can worsen
or hasten the progression of iNPH. The contribution of each
of the component diagnoses with suspected iNPH can make
the diagnosis, management, and prognostication challenging
in patients with multiple comorbidities and advancing age.
About 75% of the patients with iNPH also have cerebrovascular
dementia or Alzheimer’s disease.[11] Studies also show that 40–75%
of the patients with iNPH have beta‑amyloid or other typical
histological findings of Alzheimer’s disease.[13] The CSF shunting
would still improve gait, while cognitive improvement is less
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S409
Table 3: Clinical and radiological features of iNPH
Gait‑ At least two of the following:
Decreased step height
Decreased step length
Decreased cadence (speed of walking)
Increased trunk sway during walking
Widened standing base
Toes turned outward on walking
Retropulsion (spontaneous or provoked)
En bloc turning (turning requiring three or more steps for 180°)
Impaired walking balance, as evidenced by two or more
corrections out of eight steps on tandem gait testing
Cognition‑ at least two of the following:
Psychomotor slowing (increased response latency)
Decreased fine motor speed
Decreased fine motor accuracy
Difficulty dividing or maintaining attention
Impaired recall, especially for recent events
Executive dysfunction, such as impairment in multistep
procedures, working memory, formulation of abstractions/
similarities, insight
Behavioral or personality changes
Urinary incontinence‑
At least one of the following:
Episodic or persistent urinary incontinence not attributable to
primary urological disorders
Persistent urinary incontinence
Urinary and fecal incontinence
Or any two of the following:
Urinary urgency as defined by the frequent perception of a
pressing need to void
Urinary frequency as defined by more than six voiding episodes in
an average 12‑h period despite normal fluid intake
Nocturia as defined by the need to urinate more than two times in
an average night
Other brain imaging findings may be supportive of an iNPH
diagnosis but are not required for a probable designation:
A brain imaging study performed before the onset of symptoms
showing smaller ventricular size or without evidence of
hydrocephalus
Radionuclide cisternogram showing delayed clearance of
radiotracer over the cerebral convexities after 48‑72 h
Cine MRI study or other technique showing increased ventricular
flow rate
A SPECT‑acetazolamide challenge showing decreased
periventricular perfusion that is not altered by acetazolamide
common. Table 4 lists the differential diagnoses which may both
masquerade an underlying diagnosis of iNPH or coexist with it.
Associated visual and hearing impairment, obesity, coronary
artery disease, chronic pulmonary disease, musculoskeletal
degenerative diseases, and vestibular disorders may aggravate
other symptoms and shift attention from the diagnosis of iNPH.
Decision‑Making
In case of diagnostic confusion, more invasive tests like
CSF Infusion Testing,[34] external lumbar drainage,[21] and
intracranial pressure monitoring [35] can be performed
depending upon the expertise of the center. However, the
 Vibha and Tripathi: Evaluation NPH

simple tap test in conjunction with clinical and imaging The flowchart [Figure 2] describes the decision workflow and
features can be helpful in deciding in a majority of the cases. follow‑up in these patients.

Figure 2: Decision flowchart

Table 4: Differential diagnosis of iNPH

Diagnosis Differentiating clinical feature (s) Supporting investigation
Neurodegenerative disorders
Alzheimer’s disease Starts with cognitive disturbances. Urinary and gait Cerebral atrophy on imaging
disturbances in moderate to advanced disease
Parkinson’s disease Rest tremor, unilateral onset, improved gait with Normal imaging
external stimuli
Frontotemporal dementia Behavioral changes precede other features Frontotemporal atrophy in imaging
Lewy‑body dementia Visual hallucinations, delusions, fluctuating cognition Supportive neuroimaging and PET/DaTSCAN
Corticobasal degeneration Asymmetric parkinsonism with alien limb phenomenon, Supportive neuroimaging and PET/DaTSCAN
apraxia
Progressive Supranuclear PalsyPseudobulbar palsy, supranuclear upward gaze paresisBrainstem atrophy on MRI
Vascular disorders
Vascular Parkinsonism and Presence of focal weakness or signs, history of stroke, MRI showing vascular ischemic demyelination
vascular cognitive impairment and vascular risk factors without hydrocephalus
Other causes of hydrocephalus
Aqueductal stenosis Features of raised intracranial pressure like headache Confirmation of obstruction on MRI
and visual disturbances
Intraventricular Features of raised intracranial pressure, papilledema, Constructive interference in steady‑state (CISS)
neurocysticercosis (NCC) seizures sequence in MRI may show the NCC
Infectious
AIDS dementia complex Psychomotor slowing, impairment of memory and HIV ELISA should be done with suspected iNPH
concentration, gait impairment due to HIV myelopathy
Neurosyphilis Behavior, gait, and cognitive changes CSF VDRL should be done with suspected iNPH
Chronic meningitis May present with gait, urinary and cognitive changes CSF pleocytosis, hypoglycorrhachia suggests
which are rapidly progressive infection CSF for abnormal cells, India ink stain. and
TB GeneXpert should be done
Others
Vitamin B12 deficiency Can present with cognitive and gait disturbances Vitamin B12 should be done with suspected iNPH
Hypothyroidism Can present with cognitive and gait disturbances Thyroid function should be done with suspected
iNPH
Degenerative arthritis in lower Evidence of pain and swelling in joints with a disability Consistent radiology of joints
limbs that can be explained by an orthopedic problem
Cervical stenosis and Presence of pyramidal weakness, significant motor Supportive MRI spine
myelopathy disability with intact cognition
Peripheral vascular claudication History suggestive of peripheral vascular disease. Supportive vascular imaging
Absent peripheral pulses
Obstructive uropathy Can have progressive bladder symptoms Absence of gait and cognitive disturbances. Normal
brain imaging

S410 Neurology India | Volume 69 | Supplement 2 | November-December 2021

 Vibha and Tripathi: Evaluation NPH
An improvement by  ≥20% in the gait parameters not only
confirms the clinical suspicion of NPH but also predicts
improvement with ventriculoperitoneal (VP) shunt surgery.
If the CSF tap test is negative but clinical and radiological
suspicion is high, the possibilities are of the late stage of
the disease, insufficient volume of CSF tap, coexisting other
diagnoses, or alternative diagnosis. If the other differential
diagnosis has been excluded, and the index of suspicion is high,
these patients should undergo more invasive tests mentioned
above—the external ventricular drainage, intracerebral
pressure monitoring, and CSF volume load test. In addition,
if the radiological suspicion is also low, the need for invasive
tests is warranted before excluding the diagnosis.
The treatment of iNPH is essentially surgical. However,
medical treatment of other types of hydrocephalus has also
been tried in selective patients of iNPH and some trials are also
underway.[36] The treatment mechanism is via the modulation
of CSF production (enhanced drainage, decreased production).
For enhancing the CSF drainage, osmotic (mannitol, glycerol,
isosorbide), as well as loop diuretics, have been used in the
past.[37,38] However, the current use is limited to secondary
and high‑pressure hydrocephalus.[39] For decreasing CSF
production, acetazolamide, a carbonic anhydrase inhibitor,
has been shown to reduce the production of CSF by inhibiting
the carbonic anhydrases present within the choroid plexus
of the brain as well as preventing aquaporin‑based water
conductance.[40] Although there are no clinical trials to support
its use, they may be used in patients waiting for surgery to
sustain benefit after a tap test.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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 Review Article
Access this article online
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Website:
www.neurologyindia.com
DOI:
10.4103/0028-3886.332277
Department of
Neurosurgery, All India
Institute of Medical
Sciences, Ansari Nagar,
New Delhi, India
*Authors contributed
equally
Address for
correspondence:
Dr. Vivek Tandon,
Department of
Neurosurgery, Room
No. 720, CN Center,
All India Institute of
Medical Sciences, Ansari
Nagar, New Delhi, India.
E‑mail: drtandonvivek@
gmail.com
© 2021 Neurology India, Neurological Society of India | Published by Wolters Kluwer - Medknow S413
Comparison of Programmable and
Non‑Programmable Shunts for
Normal Pressure Hydrocephalus:
A Meta‑Analysis and Trial Sequential
Analysis
Varidh Katiyar*, Ravi Sharma*, Vivek Tandon, Kanwaljeet Garg, Priya Narwal,
P Sarat Chandra, Ashish Suri, Shashank S Kale
Abstract:
Background: The use of programmable ventriculoperitoneal shunt (P‑VPS) in idiopathic normal pressure
hydrocephalus (iNPH) has increased over the last two decades, however, there is no definitive evidence to
favor them over non‑programmable VPS (NP‑VPS). Thus, there is a growing need for studies comparing
these two procedures for their efficacy and safety profile in iNPH.
Objective: In this study, we attempt to quantitatively summarize the findings of all the prospective and
retrospective studies that have directly compared the P‑VPS and NP‑VPS in terms of efficacy, complications,
or overall healthcare expenditure.
Methods: A systematic search was performed of PubMed, the Cochrane Library databases, and Google
Scholar for studies till June 2021 comparing the outcomes of P‑VPS with NP‑VPS. Four studies were finally
included in the quantitative analysis. A trial sequential analysis was done to evaluate the need for further studies.
Results: The total rates of subdural collection (odds ratio (OR) 1.03; 95% Confidence interval (CI): 0.73–1.46;
P = 0.85; I2 = 12%) as well as surgically evacuated subdural collection (OR 0.46; 95% CI: 0.14–1.55; P = 0.21;
I2 = 75%) were not significantly different for P‑VPS compared to NP‑VPS with pooled data. Similarly, the rate
of postoperative infection was found to be similar between the two types of VPS (OR 0.98; 95% CI: 0.39–2.5;
P = 0.97; I2 = 0%). The trial sequential analysis (TSA) for the need of surgical evacuation of subdural collection
and shunt revision revealed that the meta‑analysis of the currently accrued information is not conclusive.
Conclusions: Though, associated with higher initial costs, P‑VPS does not seem to result in increased
healthcare costs in the long run while enabling the surgeon to titrate the opening pressure and avoiding
additional surgical procedures like shunt revision or evacuation of subdural collection at least theoretically.
However, further trials with a greater sample size are needed to confirm these findings as the current accrued
information size is insufficient to reach an unequivocal verdict.
Key Words:
Healthcare cost, non‑programmable VP shunt, normal pressure hydrocephalus, NPH, programmable VP shunt
Key Message:
Our analysis of the existing literature shows that P‑VPS is a preferable option in iNPH in comparison to NP‑VPS
as it has lesser complication rates, thereby, reducing the subsequent healthcare costs. And, more Level I or
II studies are needed to conclusively establish the superiority of P‑VPS over NP‑VPS.
M ultiple surgical options like
ventriculoperitoneal shunt (VPS),
ventriculoatrial shunt (VAS), lumboperitoneal
paucity of literature comparing the different
surgical options, however, the VPS is the most
commonly performed surgical procedure.[2,3]
shunt (LPS), and endoscopic third ventriculostomy
(ETV) exist for the treatment of idiopathic normal
How to cite this article: Katiyar V, Sharma R,
pressure hydrocephalus (iNPH).[1] There is a
Tandon V, Garg K, Narwal P, Chandra PS, et al.
Comparison of Programmable and Non-Programmable
This is an open access journal, and articles are distributed under the terms Shunts for Normal Pressure Hydrocephalus: A Meta-
of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 Analysis and Trial Sequential Analysis. Neurol India
License, which allows others to remix, tweak, and build upon the work 2021;69:S413-9.
non‑commercially, as long as appropriate credit is given and the new
creations are licensed under the identical terms. Submitted: 11‑Jul‑2021 Revised: 20‑Aug‑2021
Accepted: 25‑Sep‑2021 Published: 11-Dec-2021
For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com
 Katiyar, et al.: P‑VPS vs NP‑VPS for NPH
In comparison to ‘flow‑regulated’ valves, most VPS utilize
‘pressure regulated’ valves which can further be classified
into programmable VPS  (P‑VPS) and non‑programmable
VPS  (NP‑VPS), based on the ability to regulate the valve
opening pressure (OP) after VPS implantation to titrate it
according to the observed evidence of over‑drainage or
under‑drainage of the cerebrospinal fluid (CSF).[3–5] With the
increase in the use of P‑VPS over the last two decades, there
is a growing need for studies comparing these two diversion
options for their efficacy and safety profile in iNPH. On one
hand, the P‑VPS is reported to have lower complication rates,
while on the other, it is associated with a significantly higher
initial cost.[1,6,7] To ascertain the cost‑effectiveness of the use of
P‑VPS, the estimates of efficacy and safety need to be evaluated
by comparative trials taking into account the total health
expenditures rather than just the initial cost. However, the
literature is lacking in this regard.[1] In this study, we attempt
to quantitatively summarize the findings of all the prospective
and retrospective studies that have directly compared the
P‑VPS and NP‑VPS in terms of efficacy, complications, or
overall healthcare expenditure.
Methods
Searching relevant literature
A medical reference librarian developed and executed a
comprehensive literature search of PubMed, Ovid MEDLINE
In‑Process and Other Non‑Indexed Citations, Ovid MEDLINE,
Ovid Embase, Ovid Cochrane Central Register of Controlled
Trials, Ovid Cochrane Database of Systematic Reviews,
Scopus, and Google Scholar from the inception of these
libraries till June 2021. To encompass more modern treatments
of iNPH, the search was limited to manuscripts in the
English language. The following search terms were used:
“hydrocephalus,” “normal pressure hydrocephalus,” “NPH,”
“iNPH,” “iNPH treatment,” “programmable shunt,” “VPS,”
“VP shunt,” “Ventriculoperitoneal shunt,” “programmable,”
“non‑programmable,” and “fixed pressure” in appropriate
combinations. The studies were screened for relevance using
their titles followed by their abstracts. References of relevant
studies were utilized to supplement the initial search. The
relevant articles filtered in at this stage were read in full and
evaluated according to our inclusion criteria.
Study eligibility criteria
Prospective and retrospective studies comparing P‑VPS and
NP‑VPS in terms of subdural collection, postoperative infection,
shunt obstruction, and need for shunt revision were included.
According to the Population, Intervention, Comparison,
O-Outcome  (PICO)  format, our patient population  (P)
included adults with iNPH undergoing P‑VPS placement as an
intervention (I) in comparison (C) to NP‑VPS placement, and
were assessed for outcomes (O) like subdural collection, need
for shunt revision, and aggregate healthcare costs. Case reports,
review articles, and letters to editors were excluded. The study
eligibility was assessed by two independent observers (RS and
KG) and any disagreements were resolved with the opinion of
a third independent observer (VT).
Data compilation process
The variables of interest were identified and data were extracted
and entered into MS Excel by an independent reviewer (AC),
S414 Neurology India | Volume 69 | Supplement 2 | November-December 2021
verified by two other independent reviewers (VK and RS). In
case of disagreement, the opinion of the fourth reviewer (VT)
was upheld. The variables extracted from the studies included
“Subdural hematoma,” “Subdural hygroma,” “Postoperative
infection,” and “Reoperation rate” apart from the demographic
data. A few studies did not report subdural hematoma (SDHm)
and hygroma  (SDHg) separately. For the purpose of this
meta‑analysis, the subdural collection was defined as either
SDHm or SDHg. The variables reported uniformly across
the studies were included in the quantitative synthesis. This
included the type of device investigated, number of patients,
sex and age distribution, SDHm/SDHg, postoperative infection
rates, and rate of revision surgery.
Data analyses
The Preferred Reporting Items for Systematic Reviews and
Meta-Analyses (PRISMA) guidelines were followed throughout
to conduct and report the results of this analysis by removing
duplicates and categorizing the articles using Endnote X9. The
meta‑analysis was done using Review Manager 5.4 (The Nordic
Cochrane Center, The Cochrane Collaboration, Copenhagen,
Denmark, 2014 Q5). The quantitative synthesis was restricted
to outcomes reported by at least three studies which was
summarized using forest plots. The outcomes reported by only
two studies were assessed qualitatively and summarized using
odds ratio plots. The heterogeneity between the studies was
calculated using the I2 measure of the amount of heterogeneity.
A P value of less than < 0.05 was considered to be statistically
significant. A random‑effects model was used to analyze the data,
as the studies varied in terms of patient demography, treatment
allocation thresholds, baseline etiologic parameters, and follow‑up
time at which the complications and infection were measured. The
certainty of the evidence was assessed using the GRADEpro tool.
A funnel plot was made to assess the publication bias.
Trial sequential analysis (TSA) was performed for the
need for evacuation of subdural collection (TSA software
version 0.9.5.10 Beta, Copenhagen Trial Unit, Center for Clinical
Intervention Research, Rigshospitalet, Copenhagen, Denmark).
For calculating the required cumulative sample size, alpha
spending boundary, and futility cone on TSA, we set the type 1
error of 5% and power of 80%.
Results
Literature search
The initial literature search was done on PubMed using
keywords (iNPH OR NPH OR normal pressure hydrocephalus)
AND  (CSF shunt OR CSF diversion OR shunting OR
programmable OR non‑programmable OR fixed pressure)
yielded 2,334 articles. On screening these articles, three
duplicates were removed; 2,331 articles were assessed for
eligibility and 48 full articles were thoroughly reviewed in
light of the above‑mentioned PICO criteria. Four full articles
meeting all eligibility criteria were included in the qualitative
and quantitative synthesis.[6–9] The search process and selection
of articles for qualitative and quantitative analysis have been
shown in the PRISMA flow diagram [Figure 1].
Study characteristics
The type of programmable and non‑programmable shunts
used in the studies are elaborated in Table 1. The certainty of
 Katiyar, et al.: P‑VPS vs NP‑VPS for NPH

Figure 1: PRISMA chart showing the selection process of studies included in the final analysis

Table 1: Summary of the characteristics of the studies included in this meta‑analysis

Authors and year Study design No. of patients Follow‑up duration Shunt types
Sæhle et al. 2014[10] Prospective RCT 68 6 months Codman Hakim programmable valve
The 20‑4 group: 34
The 12 group: 34
Serarslan et al. Retrospective 110 72 months Adjustable : 30
2016[7] Non‑adjustable : 80
Sundström et al. Prospective quality 1846 12 months Adjustable : 1636
2018[11] registry Strata (1027)
Codman Hakim programmable valve (486)
Codman Hakim programmable valve with
SiphonGuard (56)
Codman Certas programmable valve (18)
Miethke (5)
Fixed : 203
Delta (58)
Codman Hakim precision fixed‑pressure valve (136)
Rinaldo et al. 2019[6] Retrospective 348 27.6±34.7 months Programmable: 98
Fixed: 250

evidence and summary of findings for the outcomes that were Subdural collection (SDHm and SDHg)
quantitatively synthesized in the meta‑analysis have been SDHm
summarized in the GRADEpro table [Table 2]. Additionally, Only two studies reported the incidence of SDHm and
to evaluate the publication bias, a funnel plot was made for proportion requiring surgical evacuation, and thus, the
the outcomes with more than two studies. meta‑analysis was not done. There were 16 instances of
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S415
 Katiyar, et al.: P‑VPS vs NP‑VPS for NPH

SDHm out of a total of 114 NP‑VPS compared to 5 out of 64

P‑VPS [Figure 3a]. A surgical evacuation was required in 11

(0.73-1.46) 42 fewer to 62 more) VERY LOW

(0.14-1.55) 76 fewer to 43 more) VERY LOW

(0.39-2.50) 25 fewer to 56 more) VERY LOW

Certainty
and 2 patients, respectively [Figure 3b].
Table 2: GRADEpro table showing the certainty assessment and pooled effects for comparison of various outcomes between P‑VPS and NP‑VPS

OR 1.03 4 more per 1,000 (from ⨁○○○

OR 0.46 47 fewer per 1,000 (from⨁○○○

OR 0.98 1 fewer per 1,000 (from ⨁○○○

Subdural collection
Most of the studies presented the results with both SDHm
Absolute (95% CI)
and SDHg combined, which we have termed as a subdural
collection. The total rate of the subdural collection was 17.82%
among the NP‑VPS which reduced to 11.0% for P‑VPS while the
rate of those requiring surgical drainage was 9.01 and 3.23%,
respectively. However, the difference was not significant for
Effect

the subdural collection rate with pooled OR of 1.03 (95% CI:

0.73–1.46; P = 0.85; I2 = 12%, fixed effects) [Figure 4a] as well
as surgically evacuated subdural collection (OR 0.46; 95% CI:
(95% CI)
Relative

0.14–1.55; P = 0.21; I2 = 75%, random effects) [Figure 4b].

Postoperative infection, shunt obstruction, and need for shunt

revision
Programmable Non‑programmable

The rate of postoperative infection was found to be similar

95/533 (17.8%)

48/533 (9.0%)

15/364 (4.1%)

between the two types of VPS; 4.12% in NP‑VPS and 3.7% in

shunt

the P‑VPS with a pooled OR of 0.98 (95% CI: 0.39–2.5; P = 0.97;

I2 = 0%, fixed effects) [Figure 4c]. The reduction in the chances
No of patients

of shunt obstruction was seen with the use of P‑VPS with a

total rate of 3.79% compared to 7.75% in NP‑VPS. However, the
pooled effects were not calculated in view of only two studies
194/1764 (11.0%)

57/1764 (3.2%)

reporting this outcome [Figure 3c]. There was a need for shunt

6/162 (3.7%)

revision in 26.97% of the patients with NP‑VPS compared to

shunt

10.16% of P‑VPS. The difference observed was significant in

both the studies reporting this outcome [Figure 3d].

Healthcare cost
Two studies reported the details of the overall healthcare cost
considerations

in the two types of VPS. None of the studies found a significant

association

association

difference in the overall cost of long‑term treatment, though

the initial cost of P‑VPS was higher [Figure 5].
Strong

Strong
Risk of InconsistencyIndirectness ImprecisionOther

None

Trial sequential analysis

TSA was done for the primary outcome of surgical evacuation
Not serious Serious

Not serious Serious

Not serious Serious

of subdural collection. TSA for the need of surgical

evacuation of subdural collection [Figure 6] revealed that
CI: Confidence interval; OR: Odds ratio; SMD: Standardized mean difference

the meta‑analysis of the currently accrued information is

not conclusive and a total cumulative sample size of 4,761 is
required for a conclusion with reasonable certainty. The high
Certainty assessment

heterogeneity observed is responsible, in part, for the large

sample size required.

Discussion
Serious Not serious
Serious Serious

Serious Serious

The management of iNPH remains challenging despite

improvement in clinico‑radiological evaluation of the disease
as the understanding of the pathogenesis of the disease is still
bias

incomplete.[2,8,9,12] However, after appropriate radiological

and clinical evaluation of the disease, a simple CSF diversion
Subdural collection‑surgery

procedure may provide adequate relief in the symptomatology.

2297 (3 Observational)

2297 (3 Observational)

Among the currently available CSF diversion procedures,

Participants (Studies)

Postoperative infection

VPS still remains the most widely utilized. Currently, P‑VPS

Subdural collection

is being increasingly used for the management of iNPH as it

Observational)
526 (1 RCT, 2

allows for better control of CSF drainage due to the ability to

modify OP non‑invasively. This, in turn, might decrease the
morbidity by reducing the need for evacuation of the subdural
collection as well as shunt revision surgery. Therefore, with the
advent of P‑VPS, the complication profile of the shunt surgery

S416 Neurology India | Volume 69 | Supplement 2 | November-December 2021

 Katiyar, et al.: P‑VPS vs NP‑VPS for NPH

a b c

Figure 2: Funnel plots to show the publication bias for the following outcomes, (a) Subdural Collection, (b) Subdural collection: Surgical evacuation, (c) Postoperative
infection

d
Figure 3: Odds ratio plots showing a comparison between P‑VPS and NP‑VPS for the rate of (a) Subdural hematoma, (b) Surgical evacuation of subdural hematoma,
(c) Shunt obstruction, (d) Revision surgery

for iNPH is expected to improve, though it may be associated
with increased initial cost over the NP‑VPS.[3,7,10,13]
In a previously published single‑arm meta‑analysis evaluating
different CSF diversion procedures, it was found that the
pooled rate of the subdural collection (9% vs 12%) and shunt
revision surgery (12% vs. 32%) were lower in the studies
evaluating P‑VPS compared to the NP‑VPS studies. However, it
is not appropriate to compare the pooled results of single‑arm
meta‑analyses of the two treatment modalities to draw a
sound conclusion about their relative performance as the data
regarding the safety and efficacy profile are derived from
different studies with different methodologies. The authors did
not include any study which compared the two types of VPS
directly.[1] To answer this pertinent question, a meta‑analysis of
the studies directly comparing P‑VPS with NP‑VPS for iNPH
was, thus, performed. Additionally, TSA was conducted to
understand the sufficiency of the currently accrued evidence in
the meta‑analysis and consequently the need for further trials
to ascertain the better treatment.
We did not find any significant difference between the
two types of valves in reducing the incidence of subdural
collection (including both SDHg and SDHm) in the pooled
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S417
results. Similarly, the proportion of subdural collection
requiring surgical drainage was also not different between
the two groups. Sundström et al.[11] further noted in their
post hoc analysis that they could have avoided a greater
proportion of surgical management for subdural collections
by OP adjustments in the P‑VPS arm. Rinaldo et al.,[6] on the
other hand, found the rate of surgical drainage for subdural
collections marginally higher in the P‑VPS group contrary to
the other studies which might be attributable to the ‘surgeon’s
preference’ bias. In line with the above findings, the TSA also
revealed contradictory findings with the sequential addition
of Sundström et al.[11] followed by Rinaldo et al.[6] for the
requirement of surgical evacuation. Further trials with a clear
definition of surgical indication in the subdural collection are
needed to explore this putative benefit of P‑VPS.
Similarly, P‑VPS offers non‑invasive means vis‑a‑vis revision
surgery for the management of other milder manifestations of
over‑ or under‑drainage as well. Consequently, the repertoire
of indications for shunt revision is limited to only shunt
malfunction or infection. On the other hand, the use of NP‑VPS
provides shunt revision as the only choice for persistent
symptoms of over‑ or under‑drainage, even if mild in addition to
the complications associated with malfunction or infection.[10,14,15]
 Katiyar, et al.: P‑VPS vs NP‑VPS for NPH

c
Figure 4: Forest plots showing a comparison between P‑VPS and NP‑VPS for the rate of (a) Subdural collection (SDHm and SDHg), (b) Surgical evacuation of subdural
collection (SDHm and SDHg), (c) Postoperative infection

Figure 5: Odds ratio plot showing a comparison between P‑VPS and NP‑VPS for the overall healthcare cost per patient

initial cost of P‑VPS makes them seem less cost‑effective at the

face value. But a decrease in the need for re‑hospitalization
and surgical intervention may be sufficient to offset the
cost‑effectiveness. Both the studies included for healthcare
costs find a minimal difference in the overall costs after taking
into account the cost associated with surgical management of
shunt‑related complications.[6,7] Agarwal et al.[13]found P‑VPS to
be in fact more cost‑effective than their NP‑VPS counterparts;
an effect more prominent among the patients with NPH. Lee
et al.[16] in their study on the management of hydrocephalous
secondary to aneurysmal subarachnoid hemorrhage have, in
fact, shown savings of $647 by the use of P‑VPS over NP‑VPS
as a lesser number of shunt revisions were required in the
P‑VPS group.

To the best of our knowledge, this is the first systematic review

Figure 6: Trial sequential analysis (TSA) for the need of surgical evacuation
of subdural collection (SDHm and SDHg) showing the insufficiency of accrued
information
In the consideration between P‑VPS and NP‑VPS, the decision
should be guided by their effect on symptom improvement,
rates of various complications, and healthcare costs. The
findings of our meta‑analysis suggest that the two types of VPS
perform more or less similarly as far as symptom improvement
or complication rates are concerned. The primary difference
between the two arises in relation to the management of the
complications which can be done non‑invasively in P‑VPS
saving additional costs of surgical management including
shunt revision and surgical drainage of subdural collection.
Though, in the context of similar safety and efficacy, the higher
and meta‑analysis of the studies directly comparing P‑VPS and
NP‑VPS which is a very pertinent question from the current
standpoint of iNPH management. We have not only attempted
to answer this question quantitatively with a meta‑analysis
but also brought forth the lacunae in the pooled evidence by
performing TSA which will guide the future trial designs and
sample size.
Though there is a lack of clear evidence proving the superiority
of P‑VPS over NP‑VPS due to the paucity of comparative
literature, the possibility of non‑invasive management of
over‑drainage or under‑drainage afforded by P‑VPS is a
logically obvious advantage. Thus, even in the absence
of any difference in either symptomatic improvement or
complications, if the overall healthcare cost remains the same

S418 Neurology India | Volume 69 | Supplement 2 | November-December 2021

 Katiyar, et al.: P‑VPS vs NP‑VPS for NPH
as suggested by the current evidence, the use of P‑VPS remains
preferable.
Limitations‑  There are some limitations of our study in
view of the fact that the studies pertaining to the question
of interest and qualifying for inclusion were very few and
diverse methodologically despite extensive database search.
The P‑VPS use in iNPH is favored by the surgeons and
patients alike, due to the obvious advantage of being able
to alter the pressure, if need be. A detailed analysis of the
financial and non‑financial burden associated with the visits
and the radiology required for alteration of OP would have
given a greater insight regarding the cost‑benefit analysis
of P‑VPS. However, none of the studies we reviewed
had commented on the said issue and consequently, we
could not include it in our analysis. In the present times,
despite the lack of Level I evidence to support P‑VPS over
NP‑VPS, new Randomised controlled trials (RCTs) to prove
the superiority of one over the other may not be feasible.
Probably due to the above reason, limited literature is
available pertaining to this topic. Thus, for several outcomes
in our meta‑analysis, we had only two studies which
decreased the robustness of our analyses.
Conclusions
The use of P‑VPS instead of traditional NP‑VPS for the
treatment of iNPH is currently based on the loco‑regional
and surgeon preference in the absence of definitive evidence
in favor. Though, associated with higher initial costs, P‑VPS
does not seem to result in increased healthcare costs in the long
run while decreasing the morbidity associated with additional
surgical procedures like shunt revision or evacuation of
subdural collection at the same time. However, further trials
with a greater sample size are needed to confirm these findings
as the current accrued information size is insufficient to reach
an unequivocal verdict.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
Conflicts of interest
On behalf of all the contributors, the corresponding author
states that there is no conflict of interest.
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6. Rinaldo L, Bhargav AG, Nesvick CL, Lanzino G, Elder BD. Effect
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 Review Article

Access this article online

Quick Response Code:
Post Traumatic Hydrocephalus:
Incidence, Pathophysiology and
Outcomes
Phelix Rufus, Ranjith K. Moorthy, Mathew Joseph, Vedantam Rajshekhar
Website:
www.neurologyindia.com

DOI: Abstract:
10.4103/0028-3886.332264
Background: Post‑traumatic hydrocephalus (PTH) is a sequel of traumatic brain injury (TBI) that is seen
more often in patients undergoing decompressive craniectomy (DC). It is associated with prolonged hospital
stay and unfavorable outcomes.
Objective: To study the incidence and risk factors for development of PTH in patients undergoing DC in our
institution and to review the literature on PTH with respect to incidence, risk factors, pathophysiology, and
outcomes of management.
Methods: Data from 95 patients (among 220 patients who underwent DC for TBI and fulfilled the inclusion
criteria) over a 5‑year period at Christian Medical College, Vellore were collected and analyzed to study the
incidence and possible risk factors for development of PTH. A review of the literature on PTH was performed
by searching PUBMED resources.
Results: Thirty (31.6%) out of 95 patients developed post‑traumatic ventriculomegaly, of whom seven (7.3%)
developed symptomatic PTH, necessitating placement of ventriculoperitoneal shunt (VPS). No risk factor
for development of PTH could be identified. The reported incidence of PTH in the literature is from 0.07%
to 29%, with patients undergoing DC having a higher incidence. Younger age, subarachnoid hemorrhage,
severity of TBI, presence of subdural hygroma, and delayed cranioplasty after DC are the main risk factors
reported in the literature.
Conclusions: PTH occurs in a significant proportion of patients with TBI and can lead to unfavorable outcomes.
PTH has to be distinguished from asymptomatic ventriculomegaly as early as possible so that a CSF diversion
procedure can be planned early during development of PTH.
Key Words:
Cerebrospinal fluid dynamics, post‑traumatic hydrocephalus, risk factors, subdural hygroma, traumatic brain
injury, traumatic subarachnoid hemorrhage

Key Messages:
Post‑traumatic hydrocephalus (PTH) occurs in a significant number of patients following TBI and can have
an impact on the outcome of TBI. Early recognition and differentiation from post‑traumatic ventriculomegaly
are essential. Ventriculoperitoneal shunt is the procedure of choice in PTH.

P ost‑traumatic hydrocephalus (PTH), a sequel

of traumatic brain injury (TBI), refers to
an excessive accumulation of cerebrospinal
fluid  (CSF) within the ventricles as a result of
Department of altered CSF dynamics following TBI. PTH has
Neurological Sciences, been reported in 0.7%–29% of patients following
Christian Medical TBI.[1‑5] In patients undergoing decompressive
College, Vellore, craniectomy  (DC), PTH has been reported in
Tamil Nadu, India 4%–54% of patients.[5‑26] The incidence of PTH
among children with TBI is lower at 0.07%–1%.[27‑29]
Address for In children with severe TBI, the incidence has been
correspondence: reported to be up to four to fivefold higher.[27] The
Dr. Ranjith K. Moorthy,
Department of
Neurological Sciences, This is an open access journal, and articles are distributed under the terms
Christian Medical College, of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0
Vellore ‑ 632 004, License, which allows others to remix, tweak, and build upon the work
Tamil Nadu, India. non‑commercially, as long as appropriate credit is given and the new
creations are licensed under the identical terms.
E‑mail: ranjith@cmcvellore.
ac.in For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com
incidence of PTH among children undergoing DC
has been reported to be 40% in one series.[30] PTH
has been reported to prolong hospital stay and
treatment costs and is associated with an increased
risk of unfavorable outcomes following TBI.[29,31]
We aim to review the literature on PTH with
special emphasis on its pathophysiology and
management outcomes as well as report our
experience in the management of patients with
PTH.
How to cite this article: Rufus P, Moorthy RK,
Joseph M, Rajshekhar V. Post Traumatic Hydrocephalus:
Incidence, Pathophysiology and Outcomes. Neurol
India 2021;69:S420-8.
Submitted: 26‑Jun‑2021 Revised: 17‑Aug‑2021
Accepted: 09‑Sep‑2021 Published: 11-Dec-2021

S420 © 2021 Neurology India, Neurological Society of India | Published by Wolters Kluwer - Medknow
 Rufus, et al.: Post traumatic hydrocephalus
CMC Vellore Experience
Patients and methods
After obtaining approval from the review board of our
institution (IRB No. 12624), data on patients who underwent
DC for TBI from May 2015 to May 2020 were extracted
from a prospectively maintained database to study the
incidence and risk factors for PTH. Figure 1 shows the flow
chart for recruitment of patients into the study. During the
study period, 2403 patients with TBI were admitted in our
institution.
Ninety‑five (73 males, age: 38.6 ± 11.8 years) out of 220 patients
who underwent unilateral DC during the study period were
eligible for inclusion as they had computed tomography (CT) of
brain done ≥15 days after DC. Ventriculomegaly was defined
as Evan’s ratio >0.3. Patients with symptoms attributable to
ventriculomegaly  (new‑onset neurological deficits, raised
intracranial pressure, and fullness of the scalp defect) were
defined to have PTH, while others were termed asymptomatic
ventriculomegaly.
The following variables were studied to assess the correlation
between development of ventriculomegaly and PTH: age,
severity of TBI as determined by Glasgow Coma Scale (GCS)
score at admission, presence of subarachnoid hemorrhage,
subdural hemorrhage or contusions, effacement of basal
cisterns and third ventricle, interval between trauma and DC,
distance of medial limit of craniectomy from midline, presence
of subdural hygroma (SDG), and postoperative meningitis.
Results
Thirty  (31.6%) out of 95  patients were detected to have
ventriculomegaly at a median interval of 140 (IQR: 50.5–359)
days from DC. Ventriculomegaly was detected ≤1 month after
DC in five (16.7%) patients, 1–6 months after DC in 12 (40%)
Figure 1: Flow chart of patient selection criteria
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S421
patients, and >6 months after DC in the remaining 13 (43.3%)
patients.
Seven (23.3%) of the 30 patients with ventriculomegaly were
symptomatic and fulfilled the criteria for PTH. The incidence of
PTH was 7.3% (7/95) in our patient population. Three patients
had headache, five had altered sensorium with worsening
of GCS score, and two had presented with progressively
worsening pseudomeningocele.
All seven patients with PTH underwent ventriculoperitoneal
shunt (VPS) (programmable valve in four and fixed medium
pressure valve in 3 patients), following which 71.4% (n = 5)
improved at a median follow‑up of 24  months  (IQR: 18.5–
37.5)  [Figure  2]. The 23  (76.7%) patients with asymptomatic
ventriculomegaly maintained their status at a median
follow‑up of 18  months  (IQR: 14–34.5) since the time of
DC  [Figure  3]. Cranioplasty was performed in all seven
patients within a few days after VPS. No patient developed
new‑onset ventriculomegaly in the remaining 65 patients on
further follow‑up.
There was a significant difference in the interval from DC to
detection of PTH compared to asymptomatic ventriculomegaly.
The median duration from DC to detection of hydrocephalus
in the PTH group was 76  days  (IQR: 40.5–133  days)
and 210  days  (IQR: 58–441  days) in the asymptomatic
ventriculomegaly group (P = 0.02).
There was no correlation between any of the variables studied
and development of asymptomatic ventriculomegaly or PTH
in patients undergoing DC.
In addition to the seven patients with PTH described above, six
patients who did not fulfill the inclusion criteria for this study—
unilateral DC with the evacuation of contusions (n = 2), bilateral
DC  (n  =  2), posterior fossa DC  (n  =  1), and conservatively
 Rufus, et al.: Post traumatic hydrocephalus
a c
b
d e f
Figure 2: Axial CT slices of a 25-year-old man who was admitted with moderate
TBI. (a) CT at admission showing left frontoparietal acute subdural hematoma with
midline shift. His GCS score was 9/15. He underwent left DC. (b and c) CT done
on the fourth postoperative day showing the craniectomy defect with herniation of
brain through it. Note the presence of thin interhemispheric SDG. The medial limit
of the craniectomy measured 18 mm from the midline. His GCS score at discharge
was 12/15 with aphasia and right hemiparesis. (d) CT done 2 months later when
he presented with fullness at the craniectomy site showing dilated third and lateral
ventricles. His GCS score was 11/15. A medium-pressure VPS was done. (e) CT
done 24 months following VPS showing well-decompressed ventricles and brain
having sunken into the defect. (f) He underwent cranioplasty. Postoperative CT
showing well-decompressed ventricles with cranioplasty flap in situ. His GCS score
remained 12/15 with residual aphasia and right hemiparesis.
managed TBI  (n  =  1)—underwent VPS for PTH. Thus, the
incidence of PTH in the entire cohort was 13  (0.5%) among
2403 patients with severe and moderate TBI managed during
the study period.
Review of literature
Ventriculomegaly post TBI and PTH
Excessive accumulation of CSF within the ventricular system
results in ventriculomegaly. Ventriculomegaly resulting from
volume loss following brain parenchymal injury does not cause
symptoms requiring neurosurgical intervention. In contrast,
ventriculomegaly associated with clinical symptoms would
be better defined as PTH (as in our series), and these patients
are candidates for neurosurgical intervention. PTH has been
reported to occur as early as 3  weeks post injury.[10,11] Most
authors reported PTH to occur from a few weeks to up to
6 months, but no definite timeline has been reported to define
PTH.[8‑11,16,18,28,32] In our experience, no patient developed PTH
requiring intervention beyond 6 months of DC.
Ventriculomegaly has been diagnosed using Evan’s
index (>0.3), frontal horn index, and Gudeman’s criteria.[33] The
ratio of frontal horn diameter to the maximal anteroposterior
diameter of the skull on CT in the same slice has been proposed
as an alternative in patients undergoing DC as the other
measurements may not be reliably performed in the presence
of a unilateral craniectomy defect.[34]
It is difficult to rely on the clinical features of patients with
post‑traumatic ventriculomegaly in several instances.
Alteration in the sensorium or features of bifrontal dysfunction
may be seen as sequelae of TBI. The following clinical
features will help in diagnosing PTH in patients with
post‑traumatic ventriculomegaly: features of raised ICP,
development of new‑onset gait disturbances or urinary
S422 Neurology India | Volume 69 | Supplement 2 | November-December 2021
a b c
d e
Figure 3: Admission and postoperative images of a 44-year-old man who was
admitted with moderate TBI. (a) Axial CT at admission showing diffuse brain injury
with right frontal contusion with effacement of the subarachnoid spaces. His GCS
score was 9/15. He underwent right DC. (b) Axial CT on the seventh postoperative
day showing the craniectomy defect with minimal herniation of brain through it. Note
the presence of bilateral convexity SDGs. (c) Axial CT on the seventh postoperative
day showing interhemispheric hygroma and left-sided SDG. The medial limit of the
craniectomy measured 19 mm from the midline. His GCS score improved to 15/15.
(d) CT done 7 months later when he presented for cranioplasty showing dilated
third and lateral ventricles. He had no symptoms and underwent cranioplasty. (e)
Postop axial T2W MRI done at 6 months following cranioplasty showing stable
ventriculomegaly. He had no new symptoms.
incontinence, spasticity, worsening of cognition, arrest in the
improvement of neurological status, progressively worsening
or tense pseudomeningocele post DC, or development of new
neurological deficit.[8,10]
In patients without clinical signs and progressively worsening
ventriculomegaly, lumbar infusion studies may aid in
differentiating ventriculomegaly from PTH. Patients who
had DC will need to have cranioplasty done prior to these
studies.[35,36] As patients with PTH are more likely to benefit
from CSF diversion than those with ventriculomegaly
secondary to atrophy, it is important to distinguish the two
entities.[1]
Marmarou et al. [37] in 1996 classified patients with
ventriculomegaly based on the results of CSF infusion studies.
Based on the ventricular size  (frontal horn index) and CSF
outflow resistance (R0), patients with ventriculomegaly were
classified into those with normal ICP and normal R0 (atrophic
ventriculomegaly), those with normal ICP and high R0 (defined
as  >6 mm  Hg/ml/min), and those with high ICP with or
without high R0. The latter two groups of ventriculomegaly
were defined as normal‑pressure and high‑pressure PTH,
and these would be considered for shunt placement. Patients
defined as PTH had poorer outcomes at follow‑up when
compared with those with atrophic ventriculomegaly.[37]
Nearly two decades later, De Bonis et al.[38,39] reported that
R0 >10 mm Hg/ml/min and elastance index >0.3 predicted
shunt responsiveness in patients with post‑traumatic
ventriculomegaly. Others have reported a lack of correlation
between CSF infusion studies and degree of ventriculomegaly,
though shunt responders had higher R0 values compared
to those without response to shunt. These authors also
reported that R0 values in PTH were significantly lower
than that of patients with idiopathic normal pressure
 Rufus, et al.: Post traumatic hydrocephalus
hydrocephalus  (NPH).[35] Ramesh et al.[40] observed that R0
value‑based diagnosis and management had a predictive value
of 62.5% in eight patients with PTH, and all three patients who
underwent shunt placement had high R0 values. R0 had higher
predictive values in patients with NPH or postmeningitic
hydrocephalus.[40]
Pathophysiology
In TBI, there is disruption of normal dynamic balance
between CSF production and absorption.[41,42] Clot formation
following intraventricular or subarachnoid hemorrhage results
in obstruction of CSF flow and acute hydrocephalus.[41,44]
Subsequently, adhesions in the basal cisterns and inflammation
cause impaired CSF absorption and chronic PTH.[42]
The normal dicrotic intracranial waveform is flattened in
patients with DC as there is dissipation of pressure pulse
through an open craniectomy defect. This results in decreased
volume of CSF reaching the arachnoid granulations. Moreover,
CSF flow into arachnoid granulation requires pulsatile pressure
waves due to the presence of unidirectional valves, and these
are obviated once DC is performed.[26] Post‑surgical debris and
blood also cause mechanical blockade to the flow of CSF into
the arachnoid granulations.
Subdural hygromas (SDG) after TBI and after DC occur due to
traumatic rupture of dura‑arachnoid interface and arachnoid
tearing. SDG ipsilateral to DC is due to CSF collection into
the expanded subdural space after craniectomy, whereas
contralateral and interhemispheric SDGs are due to differences
in pressure created between both the cerebral hemispheres and
disruption of normal CSF circulation. Progressive worsening of
SDGs as well as ventricular dilatation may cause obliteration
of the cortical subarachnoid spaces and an increase in R0,
promoting further CSF accumulation within the ventricular
system.[15,18,36] In contrast to these hypotheses, De Bonis et al.[17]
postulated that there is loss of external compressive forces
on the superficial veins in patients with DC. The closer the
craniectomy is to the midline, the more is this effect. This results
in increased venous outflow and thereby increased extracellular
fluid drainage, thus decreasing brain parenchymal volume and
promoting ventricular dilatation.[17]
Using perfusion‑timing analysis on magnetic resonance
imaging (MRI) of healthy subjects and TBI patients, Aso et al.[45]
postulated that TBI‑induced neuronal loss and gliosis (akin to
that occurring with normal aging) result in increased resistance
of the superficial venous system, and this initiates a vicious
cycle of CSF accumulation and further increase in resistance
of venous outflow. This could result in gradual ventricular
dilatation.
Acute hydrocephalus was observed at 24 hours in a lateral
fluid percussion rodent model, and this was attenuated by
injection of deferoxamine (an iron chelator). Intraventricular
administration of ferric chloride also resulted in acute
ventricular dilatation. Cisternal CSF analysis showed elevated
heme oxygenase‑1 following TBI that could be reduced by
deferoxamine, indicating that iron and Heme metabolites in
the subarachnoid space may contribute to the development of
PTH.[46] In another study, monocyte depletion attenuated the
development of PTH and preserved white matter integrity after
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S423
TBI in mice, indicating the role of inflammatory processes in
the development of PTH.[47] The various pathophysiological
mechanisms contributing to the development of PTH are
summarized in Figure 4.
Risk factors for PTH [Table 1]
Children aged 0–5 years were at a higher risk of developing
PTH compared to older children on the Nationwide Emergency
Department Sample database and the Kids Inpatient
Database.[27,29] In another series, children  <1  year were at
the highest risk of developing PTH.[28] Presence of subdural
or subarachnoid hemorrhage, contusion, increased injury
severity, and DC have all been reported to predispose to the
development of PTH among children.[27,30] Younger adults
have been reported to have a higher risk of developing PTH,
probably related to their injuries being more severe and the
increased chance of survival following management of severe
TBI.[10,48,49] On the contrary, increased age has been reported to
be a risk factor in other series, probably related to the increased
propensity of fibrosis and adhesions in the subarachnoid space
in these patients.[3,8]
In a large retrospective population‑based cohort study, patients
with traumatic subarachnoid hemorrhage had an approximate
threefold risk of developing PTH, compared to TBI patients
without traumatic subarachnoid hemorrhage.[44] Presence of
subdural, subarachnoid, or intraventricular hemorrhage has
been reported by others to predispose to PTH.[3,8,11,12,15,27,29]
While ipsilateral SDG disappears, interhemispheric SDG and
SDG contralateral to the side of DC precede the development
of ventriculomegaly and have been reported to be a risk factor
for PTH.[2,8,10,15‑18,49]
Bilateral or unilateral DC is an independent risk factor for
development of PTH, with 3.6  times increased risk being
reported in one series.[4,5,9,12,15‑17,32,48] In a meta‑analysis of 25
retrospective studies (n = 2402) from 1983 to 2018, the event
rate for PTH following DC in was 13%  (range: 9%–18.5%)
in adults and 37.6% in children.[23] As DC results in loss of
systolic‑diastolic pulsatile differences in intracranial pressure
as described earlier, early cranioplasty may help in restoring the
CSF dynamics. Delayed cranioplasty by >2–3 months following
DC was an independent risk factor for development of PTH
in some series.[15,18,26,28]
Increased severity of primary brain injury is an independent
predictor of PTH. Severe brain parenchymal damage results
in an increased risk of brain atrophy and ventriculomegaly.
Management of severe head injury also results in prolonged
ICU stay, development of infectious complications, and
increased need for DC.[4,8,9,12,16,27,29,32,48] Post‑traumatic cerebral
infarction and postoperative meningitis have been reported
as predictors of PTH by several authors.[8,17] Chen et al.[4]
validated a risk stratification scoring system that predicted the
development of PTH by incorporating age, severity of injury,
and DC along with other characteristics.
Outcomes of TBI with PTH
PTH has been associated with unfavorable neurological
outcomes following TBI in  >65% of patients in several
series.[2,50,51] PTH results in longer hospital stay and a longer
 Rufus, et al.: Post traumatic hydrocephalus
Figure 4: Summary of the pathophysiology of PTH
period of rehabilitation even if not associated with poorer
outcomes.[30] Disappearance of cisterna ambiens  (in 92.35%
patients), prolonged coma (>2 months) (in 77.9% patients), and
elevated plasma fibrinogen levels were identified as potential
risk factors for predicting poor outcome for PTH in one series.[50]
In our series, although the number of patients with PTH was
small, PTH did not influence the outcomes in patients once it
was treated.
Treatment options for PTH
Patients with symptomatic PTH require CSF diversion. Acute
hydrocephalus can be managed through external ventricular
drainage.[43] In chronic PTH, those who are asymptomatic or
whose symptoms cannot be reliably assessed but have high
R0 on infusion studies are candidates for CSF diversion.[37‑40]
VPS is the treatment of choice as most patients with PTH
have reduced brain compliance associated with defects in CSF
absorption.[28,34,48] Several authors have reported benefits with
fixed valves; others have reported the use of programmable
shunt systems or flow‑regulated valve systems.[10,12] Patients
with poor GCS score at the time of TBI, poor GOS score prior
to VPS placement, and those with associated meningitis
complicating TBI or following shunt placement have
unfavorable outcomes. [34,52] Due to the increased risk of
meningeal fibrosis in older patients as well as the increased
chance of restoration of CSF circulation in younger patients,
the latter group has been postulated to have more favorable
outcomes after CSF diversion procedures.[53]
The rate of shunt revision was 17.9% in a recent series, while
it was 24% in another series reporting PTH in children.[28,34]
Improvement following VPS has been reported in 50%–65%
of patients.[8,32,52‑54] In our patient cohort, nearly 70% of patients
improved after VPS, though the numbers were small and all
our patients underwent cranioplasty in addition to VPS. In
series reporting outcomes of PTH following DC, the role of
S424 Neurology India | Volume 69 | Supplement 2 | November-December 2021
cranioplasty in contributing to neurological improvement will
need to be considered.[54] Shunt‑dependent patients achieved
similar 6‑  and 12‑month outcomes as those without PTH,
underscoring the value of early diagnosis and VPS.[48] Ozoner
et al.[26] reported poorer outcomes in patients with PTH despite
VPS when compared to those without PTH (56% vs. 29.7%) at
12‑month follow‑up.
Wang et al.[53] developed a prediction model with 90.3%
sensitivity that could predict shunt responsiveness in PTH.
This incorporated age, severity of hydrocephalus, GCS
score at the time of injury, and time interval from trauma to
shunting. The rate of improved outcomes was 14.3%, 52.6%,
and 94.7% in the groups that were defined as low‑probability,
medium probability, and high probability, respectively,
based on their model. In their cohort of 66  patients with
GCS  <  12 at admission, 51.5% showed improvement after
CSF diversion.[53]
Endoscopic third ventriculostomy (ETV) has also been used
to treat PTH. The rationale is that it may restore intracranial
compliance by reducing CSF stagnation in the ventricular
system through an “internal shunt.”[55,56] Although a review of
the literature (14 patients) suggested 93% success in cases of
aqueductal obstruction due to hemorrhage in TBI, ETV may
be reserved as a primary procedure in patients with acute
hydrocephalus with aqueductal obstruction and as a secondary
procedure for patients with repeated VPS malfunction or
infection.[34,43] It has also been recommended that ETV be
attempted only in patients with raised ICP.[55] In a recent
report from India, the failure rate for ETV for PTH was 60%
and only 37% of patients showed improvement, vis‑à‑vis 73%
improvement following VPS.[34] Chrastina et al.[56] reported
favorable outcomes following ETV in six out of 11  patients
with PTH, five of whom had undergone DC. Two patients in
their series required subsequent VPS and both had unfavorable
outcomes.
 Rufus, et al.: Post traumatic hydrocephalus

Table 1: Summary of the literature on incidence and risk factors for PTH
Author (year) No. of Incidence of PTH Interval from Treatment of Risk factors for PTH
patients (n) trauma to PTH PTH
Including patients with
DC only
Ozoner et al. (2020)[26] 126 19.8% (n=25) NR VPS Delayed cranioplasty (>2 months post DC)
Su et al. (2019)[7] 143 30.1% (n=43) NR NR Age >48.5, contralateral SDG
Hu et al. (2018)[8] 183 27.3% (n=50) 3 months VPS (n=22) Age >51 years
Admission GCS <6
Intraventricular hemorrhage
Post‑trauma cerebral infarction
Postoperative meningitis
Di et al. (2018)[9] 121 19.01% (n=23) 3 weeks6 VPS (n=23) Admission GCS <6
months Intraventricular hemorrhage
bilateral DC
Nasi et al. (2018)[2] 130 28.4% (n=37) NR VPS (n=34) Interhemispheric SDG
Cranioplasty Delayed cranioplasty (>3 months after DC)
with LSAD (n=3)
Vedantam et al. 60 43.3% (n=26) 16.4 days VP shunt (n=15) Interhemispheric SDG
(2017)[10] Younger age
Kim et al. (2017)[11] 63 54% (n=34) 55 days NR Intraventricular hemorrhage
Midline shift >12 mm on initial CT, Acute
SDH >18 mm thickness
Fotakopoulos et al. 126 7.9% (n=10) NR VPS Large bone flap, Edge of DC <25 mm from
(2016)[12] midline
Subarachnoid hemorrhage
Repeated surgeries
Prolonged coma
Sinha et al. (2015)[14] 1236 7.5% (n=88) NR VPS or ETV NR
Ki et al. (2015)[15] 92 26.1% (n=24) NR NR Large craniectomy
Contralateral SDG
Honeybul et al. 166 45% (n=72) 6 months VPS (n=26) Low GCS score at admission
(2012)[16] High ICP prior to DC
SDG
De Bonis et al. 64 29.7% (n=19) NR VPS Medial limit of craniectomy <25 mm from
(2012)[17] midline
Kaen et al. (2010)[18] 73 27.4% (n=20) 2 months NR Interhemispheric SDG
Present study (CMC 95 7 (7.3%) Within six VPS None identified
‑ 2021) months
Including patients with
DC and no DC
Goldschmidt 402 with 21% (22/105 with DC) VPS Younger age
et al. (2020)[47] severe TBI
6% (18/297 without DC Higher injury severity score
Elsamadicy 1,244,087 0.07% (n=930) NR NR Age <5 years
et al. (2020)[27] (<21 years) Extended period of loss of consciousness
Hemorrhage
Presence of respiratory, thromboembolic or
neurological complications
Chen et al. (2019)[43] 23,775 0.48 (in no SAH group) 3 months NR SAH‑ Threefold increase in the risk of
‑1.95% (in SAH group) hydrocephalus
Bonow et al. (2018)[28] 91583 (<21 0.9% (n=846) Within 6 monthsVPS (n=846) Age <1 year
years) Surgery for TBI
Delayed cranioplasty (>30 days post DC)

Contd...
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S425
 Rufus, et al.: Post traumatic hydrocephalus

Table 1: Contd...
Author (year) No. of Incidence of PTH Interval from Treatment of Risk factors for PTH
patients (n) trauma to PTH PTH
Rumalla et al. (2018)[29] 1,24,444 1% (n=1265) NR VPS, External Age<5 years
(<21 years) ventricular drain Chronic neurological condition, iatrogenic
stroke
Septicemia
Subarachnoid hemorrhage, Subdural
hematoma
Open wound
Surgery for TBI
Low et al. (2013)[48] 871 2.6% (n=23) 70 days VPS Younger age
Unilateral and bilateral DC
GCS=Glasgow coma scale score, SAH=subarachnoid hemorrhage, SDG=subdural hygroma, MLS=midline shift, DC=decompressive craniectomy,
VPS=ventriculoperitoneal shunt, LSAD=lumbar subarachnoid drainage

Figure 5: Management algorithm for post-traumatic ventriculomegaly

The presence of fast flow void across aqueduct on T2‑weighted
and proton‑density MRI and its subsequent attenuation after
CSF diversion has been reported to be a favorable prognostic
factor with respect to shunt responsiveness in a series of
22 patients with PTH.[57] In this series, both patients in whom
the fast flow void persisted after VPS showed no improvement,
while 18/20 patients with variable reduction in the fast flow
void showed clinical improvement at 6‑months follow‑up.[57] A
management algorithm based on evidence from the literature
has been proposed in Figure 5.
Future directions
While optimizing the size of DC and the performance of early
cranioplasty may help in reducing the occurrence of PTH,
future studies should focus on identifying pathophysiological
mechanisms and modifiable risk factors. In the last few years,
cisternostomy has been introduced in management of TBI
based on the hypothesis that in TBI, CSF from the cisterns
enter into the brain parenchyma and the Virchow–Robin
spaces, thus resulting in cerebral edema. Opening the basal
cisterns at the time of surgery may reverse this process.
Parthiban et al.[58] recently reported the rate of PTH among
patients undergoing cisternostomy  (with or without DC)
to be 12%. It remains to be seen if cisternostomy will aid in
reducing the rate of PTH.
Conclusion
PTH occurs in a significant proportion of patients with TBI and
can lead to unfavorable outcomes. PTH has to be distinguished
from asymptomatic ventriculomegaly as early as possible so
that a CSF diversion procedure can be planned early during
development of PTH.
Acknowledgements
The authors would like to acknowledge the assistance provided
by Ms. Vijayalakshmi Kovardhan, Programmer, Department
of Neurological Sciences, Christian Medical College, in
preparation of the figures.
Financial support and sponsorship
Nil.

S426 Neurology India | Volume 69 | Supplement 2 | November-December 2021

 Rufus, et al.: Post traumatic hydrocephalus
Conflicts of interest
There are no conflicts of interest.
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 Review Article

Access this article online

Quick Response Code:
Subarachnoid Hemorrhage and
Hydrocephalus
Suchanda Bhattacharjee, Das Rakesh, Reddy Ramnadha, Panigrahi Manas1

Website: Abstract:
www.neurologyindia.com
Background: Hydrocephalus associated with subarachnoid hemorrhage is a common neurosurgical problem,
DOI: the management of which is tailor‑made to the patient. It is usually seen with an aneurysmal bleed and is
10.4103/0028-3886.332266 independent of the primary modality of treatment.
Aim: This study aimed to provide a comprehensive overview of this important association and discuss the
various available treatment modalities.
Materials and Methods: A detailed review of the literature was done on the risk factors, pathogenesis, and
treatment of hydrocephalus in the setting of subarachnoid hemorrhage.
Results: Hydrocephalus occurs in 6% to 67% of subarachnoid hemorrhage (SAH). It may present as acute,
subacute, or chronic at the time of presentation. Diagnosis is made with a plain computed tomography scan
of the brain, and the treatment is observant, temporary, or permanent cerebrospinal fluid diversion.
Conclusion: Hydrocephalus associated with SAH interferes with the outcome of SAH. It prolongs the hospital
stay, besides causing additional morbidity. The various risk factors, if present, should warn us to be vigilant,
and management is definitely not uniform and is custom made to the patients’ needs.
Key Words:
External ventricular drain, hydrocephalus, subarachnoid hemorrhage, ventriculoperitoneal shunt

Key Messages:
Hydrocephalus in a setting of subarachnoid hemorrhage is an infrequent later development. It may be acute
or chronic in nature. Many respond to temporary cerebrospinal fluid diversion, whereas some require a
permanent diversion. Meticulous treatment is required when the condition is present.

H ydrocephalus is one of the most common

complications in aneurysmal subarachnoid
hemorrhage (SAH) patients. SAH accounts for
Angiogram‑negative SAH occurs in about 15% of
all patients with SAH. According to the bleeding
pattern, angiogram‑negative SAH is categorized
5% of stroke, and the etiology in 85% remains into two groups: perimesencephalic SAH (PMH)
a ruptured aneurysm. [1] Hydrocephalus in and nonperimesencephalic SAH (non‑PMH).
SAH is a known factor for many decades now. Patients with PMH tend to experience a more
Department of Hydrocephalus in SAH was described for benign clinical course than those without PMH.
Neurosurgery, Nizam’s the first time by Bagley.[2] in 1928. Iwanowski Kim et al., [5] in their meta‑analysis, showed
Institute of Medical and Olszewski, in 1960, first reported that that hydrocephalus and shunting were more
Sciences, Hyderabad, hydrocephalus was detected after injecting an common in patients without PMH than in those
1
Department of iron–dextran complex into the subarachnoid with PMH.
Neurosurgery, spaces in dogs.[3] It contributes to a lengthy
Krishna Institute of hospital stay, increased critical care days, and Hydrocephalus in SAH may be classified as
Medical Sciences, morbidity among SAH patients. Additionally, acute, subacute, or chronic. Acute SAH develops
Secunderabad, the most common reason for readmission within 72 hours of the ictus, subacute occurs
Telangana, India after aneurysmal SAH is hydrocephalus. [4] between 3 and 7 days after the ictus, and chronic
Hydrocephalus can lead to cognitive decline and is defined as occurring after 7 days of ictus. There
Address for neurologic deterioration, even when the primary is yet another presentation that can be called
correspondence:
cause of SAH has been treated successfully. delayed chronic. In this type, the hydrocephalus
Dr. Suchanda
Bhattacharjee,
Hydrocephalus after nonaneurysmal SAH is develops much after the period of intervention of
Department of not very well documented in the literature.
Neurosurgery, Nizam’s
Institute of Medical This is an open access journal, and articles are distributed under the terms How to cite this article: Bhattacharjee S, Rakesh D,
Sciences, Punjagutta, of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 Ramnadha R, Manas P. Subarachnoid Hemorrhage
Hyderabad, Telangana, License, which allows others to remix, tweak, and build upon the work and Hydrocephalus. Neurol India 2021;69:S429-33.
India. non‑commercially, as long as appropriate credit is given and the new
creations are licensed under the identical terms. Submitted: 27‑Jun‑2021 Revised: 23-Aug-2021
E‑mail: suchandab2010@ Accepted: 22-Sep-2021 Published: 11-Dec-2021
gmail.com For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com

© 2021 Neurology India, Neurological Society of India | Published by Wolters Kluwer - Medknow S429
 Bhattacharjee, et al.: Hydrocephalus in subarachnoid hemorrhage – Risk factors and management
the aneurysm either by clipping or coiling. Acute and subacute
mostly suffice with a temporary drainage system, but chronic
is mostly shunt dependent.
Incidence
The incidence of hydrocephalus is said to be ranging from
6% to 67% in many series and meta‑analyses available in the
literature. About 6% to 45% of patients with this condition
require permanent cerebrospinal fluid (CSF) diversion
during follow‑up.[6‑14] Acute hydrocephalus develops in 15%
to 58.4%, and chronic hydrocephalus develops in 4.3% to
37% after aneurysmal SAH (aSAH).[15‑25] Almost 70% of acute
hydrocephalus progress to chronic hydrocephalus.
In our own series of 129 patients retrospectively analyzed at
the Nizam’s Institute of Medical Sciences, who underwent
clipping of aneurysm, hydrocephalus was encountered in
24 (18.60%) cases. Only external ventricular drain (EVD)
sufficed in 13 patients, and 11 patients required a permanent
shunt. Six patients who were shunted had an EVD earlier.
At the time of writing this article, senior author, Prof. Manas
Kumar Panigrahi analyzed the data at the Krishna Institute of
Medical Sciences and the data are under publication elsewhere;
in their series of 122 patients who were clipped for aneurysm,
20 (16.39%) patients required intervention for hydrocephalus.
Nine patients required EVD, and 11 patients required
ventriculoperitoneal  (VP) shunt. Thecoperitoneal shunt was
done in three cases. Five of the EVD subsequently had to be
replaced with a permanent shunt. In their series of coiling
in 95 patients, nine (9.47%) patients required intervention
for hydrocephalus, of which five patients required EVD and
four patients required VP shunt. Only a single EVD required
conversion to permanent shunt in this group. So their series
shows a lesser rate in the case of coiling that correlates with
the current literature.
The timing of the presentation of hydrocephalus after an
intervention is also not very well‑defined in the literature.
The earlier studies showed that post clipping of aneurysm,
the incidence of hydrocephalus was lesser compared with
coiling. This was thought to be because of irrigation of
SAH clots and fenestration of the lamina terminalis during
clipping.[22] Recent literature shows that hydrocephalus is
less noted post coiling. There are anecdotal reports in the
literature of hydrocephalus developing in coiled unruptured
aneurysms. The explanation for this is not clear. It has
been proposed that the hydrogel in the hydrogel‑based
coil slips into the CSF from the vascular lumen and sows
the seed for aseptic meningitis, which further leads to
absorption problems, and subsequently a communicating
hydrocephalus. Another explanation given is the increased
inflammatory response to the thrombosis of the aneurysm.
In all the reported cases of hydrocephalus in unruptured
aneurysms treated by coiling, they were larger‑sized
aneurysms of the basilar apex. Also, it was seen that the
hydrocephalus occurred as a delayed chronic variety with
the average interval being 8.5 months.[26]
The posterior circulation aneurysms have a higher incidence
and amid the anterior circulation aneurysms, the anterior
communicating artery (A.Com) complex aneurysm has the
highest incidence.
S430 Neurology India | Volume 69 | Supplement 2 | November-December 2021
Risk factors
The reason why hydrocephalus develops in certain cases
and is not a universal phenomenon in all aneurysm cases is
multifactorial.
The factors that are the main determinants of causing
hydrocephalus are
• presence of intraventricular blood,
• amount of blood in the subarachnoid space,
• location of the aneurysm,
• bad grade of SAH, and
• advanced age and hypertension.[27]
Certain studies have shown females having a higher incidence,
but the majority do not show any difference. In our experience,
we did not find gender to be a significant factor in our study,
but the rest of the factors mentioned above had a bearing in
our series too.
Pathogenesis
The hydrocephalus after SAH is usually a combination of both
communicating and noncommunicating types.
One of the hypotheses explains that the type of hydrocephalus
may be a function of the site of hemorrhage and not of the
temporal breakdown of blood in the subarachnoid space. This
may explain why ruptured posterior circulation aneurysms are
associated with higher rates of hydrocephalus as compared
with ruptured anterior circulation aneurysms. Posterior
circulation aneurysmal rupture may be more likely to cause
impaired CSF egress from the fourth ventricle and so produces
an obstructive pattern of hydrocephalus. The A.Com complex
and posterior circulation both bleed into the basal cisterns
and the intraventricular region. Thus, more is the incidence of
hydrocephalus. The low incidence rate in patients with middle
cerebral artery aneurysms may be explained by the fact that
subarachnoid blood clots are relatively scant in the contralateral
Sylvian fissure and interhemispheric fissures.[14,28]
Blood in the intraventricular space causes not only blockage but
also the overproduction of CSF. The ventricular wall also gets
damaged by the blood products leading to ventriculomegaly.
Blood in the basal cisterns causes blockage of the CSF pathway
leading to obstruction. The obstruction is anatomically at the
cisternal level beyond the outlet of the foramen of Luschka
and Magendie usually. However, when there is an aneurysm
at the proximal posterior aneurysm like the posterior inferior
cerebellar artery aneurysm, it may block the ipsilateral foramen
of Luschka. When there is significant ventricular blood, then
also the outlets of Luschka and Magendie are blocked resulting
in pan ventriculomegaly.
The other factor contributing to this pan ventriculomegaly
is absorption defect. This occurs due to the fibrosis of the
pacchionian arachnoid granules and leptomeninges following
the insult with blood products.
In another understanding, Stivaros and Jackson, explain
that in communicative hydrocephalus, there is a reduction
of compliance of the walls of large cerebral vessels, and
subsequently, a larger amount of the transmission of the
systolic wave to the brain. This systolic–diastolic pressure
 Bhattacharjee, et al.: Hydrocephalus in subarachnoid hemorrhage – Risk factors and management
difference is less compensated by the vessel. The increase
in capillary pulsatility causes a further enlargement of the
brain in systole and, consequently, a subarachnoid pressure
difference between the subarachnoid area and the ventricular
system. This causes a superficial vein occlusion and a
decrease in CSF absorption and leads to the development of
hydrocephalus. Decreased venous compliance due to increased
pressure changes the pulse pressure distribution throughout
the supratentorial space. To meet the incoming blood in the
systole, aqueduct flow increases up to 192%. This probably
improves the compliance, which leads to a reduction in the
cortical veins occlusion after the implementation of the shunt,
and this suggests that the compliance changes in the vessels
are not structural but functional.[29,30]
It has consistently been shown in innumerable studies that
the elderly with subarachnoid hemorrhage are more prone
to symptomatic hydrocephalus. This is probably because
the subarachnoid blood can be held for a longer time in the
cisterns due to slower CSF circulation and also there is more
leptomeningeal fibrosis and decreased ventricular compliance.[30]
Besides these above‑mentioned mechanisms of developing
hydrocephalus, there could be problems with the
microcirculation dynamics of CSF. Brain retraction and
manipulation of small vessels during surgical clipping can
disrupt the absorption of CSF by small vessels. Minimizing
brain retraction and the manipulation of blood vessels may be
helpful not only in reducing brain parenchyma injury but also
in maintaining CSF homeostasis.[31]
Low serum iron level is also proposed to be a cause of
hydrocephalus by Zhang et al.; Lysed erythrocyte‑induced
CSF iron overload contributes to ependymal cell death and loss
of cilia. This leads to inflammation, defective CSF dynamics,
and aggravates posthemorrhagic hydrocephalus as seen in
animal models. High levels of circulating cytokines, such as
transforming growth factor‑b1/b2, interleukin (IL)‑1, IL‑6, and
tumor necrosis factor alpha (TNF‑α) were all detected in acute
hydrocephalus following aSAH.[32,33]
The CSF levels of ferritin in patients with SAH were more than
200 times higher than in control patients in a study by Suzuki
et al.[34] They found that ferritin levels were high on Days 3 and
4 after ictus, and it contributed to chronic hydrocephalus.[34]
Clinical feature
Acute hydrocephalus usually presents with raised intracranial
pressure (ICP) along with features of meningeal irritation.
The Glasgow Coma Scale score could be poor either due to
hydrocephalus or SAH. There will be signs and symptoms
like any other presentation of raised ICP, which comprises
papilledema and altered sensorium. In chronic hydrocephalus,
there is usually a presentation with continuous headache and
irritation. In chronic hydrocephalus, there will usually be no
added signs of meningism. However, the history would be
relevant to point toward the causative etiology of SAH‑induced
hydrocephalus.
Diagnosis
A computed tomography  (CT) scan usually suffices for
diagnosis. Hydrocephalus is diagnosed when the temporal
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S431
horn (TH) diameter is greater than 2 mm along with the absence
of Sylvian and interhemispheric cistern and the absence of
cerebral sulci or the TH width is greater than 2 mm and the
frontal horn (FH) diameter to internal diameter (ID) is greater
than 0.5 (where the FH is the largest width of the frontal
horns and the ID is the internal diameter from inner‑table
to inner‑table at this level). Other features of hydrocephalus
include ballooning of lateral and third ventricles, periventricular
low density on CT (suggesting a transependymal absorption of
CSF), Evan’s ratio (the FH diameter to the maximal biparietal
diameter  [BPD] measured on the same CT slice  >0.3) or
increased bicaudate index (BCI; which is defined as the ratio of
the width of bilateral lateral ventricles at the level of the head
of the caudate nucleus to distance between inner tables of the
skull at the same level).
Magnetic resonance imaging (MRI) adds to the diagnosis with
the picking up of additive features such as thinning and/or
upward bowing of the corpus callosum on sagittal MRI.
Figure  1a and b shows a CT scan image of a patient who
developed hydrocephalus along with hemorrhage and VP
shunt after clipping, respectively.
Treatment
A VP shunt is the standard of care for hydrocephalus due to
SAH.
Acute hydrocephalus can be managed with a closed external
ventricular drainage system for a few days till the CSF dynamics
stabilizes, and a permanent shunt is not required. There may be
ventriculomegaly on radiology, but the clinical manifestation
may halt. About 70% of EVD, however, gets converted to
permanent shunt. In our series, the EVD requirement was in
15%, and the permanent shunting required was in 9%. This
was much lesser compared with the literature. About 65% of
the EVD did not require any conversion to permanent shunt.
However, EVD comes with its own set of problems. EVD may
not immediately clear the intraventricular hemorrhage (IVH),
and sometimes the catheter may get blocked by blood. It has
also been suggested that EVD could even potentially slow the
rate of IVH clearance by removing the tissue plasminogen
activator released from the clot into the CSF.
There is a differential practice regarding EVD management.
Some intermittently open it, and some adopt a continuous
opening policy. There are multiple reasons given to use a
continuously open drainage approach: the patient needs the
EVD open (1) for symptomatic hydrocephalus, (2) to clear
blood, (3) to reduce the risk of shunt occlusion, and (4) to
improve cerebral perfusion pressure. It is also believed that
clearing the blood products reduces the chance of vasospasm
and delayed infarcts. The Oslen randomized controlled trial has
on the contrary shown that opening intermittently is actually
safe and associated with lower malfunction.[35]
The decision regarding the withdrawal of EVD is also not
uniform. Some withdraw it early. This school of clinicians feels
that withdrawing it as soon as not required anymore helps in
opening the clogged CSF pathways, thereby resuming normal
flow, reducing the risk of ventriculostomy‑related infections,
 Bhattacharjee, et al.: Hydrocephalus in subarachnoid hemorrhage – Risk factors and management

a b
Figure 1: (a) Computed tomography (CT) scan of the brain showing hydrocephalus in a case of subarachnoid hemorrhage. (b) CT scan of the same patient after clipping of
anterior communicating artery complex aneurysm and ventriculoperitoneal shunt

and reducing intensive care unit stays. However, another

school of thought proposes weaning of EVD gradually. This
typically involves leaving the drain open for a prolonged
period, followed by a period of weaning, during which the
drain is raised gradually (e.g., from 10 to 15, then 15 to 20, and
then 20 to 25 cm H2O) over several days until it is eventually
clamped and discontinued.[36]

When the patient is continuously dependent on EVD, the

decision to convert to a permanent CSF diversion is required.
VP shunt is the first treatment of choice. When there is
shunt failure, which is quite a common phenomenon in
neurosurgical practice, the VP shunt is usually revised, and
if the peritoneum is not suitable for implantation, then an
alternative destination such as the right atrium or pleura is
considered.
Endoscopic third ventriculostomy  (ETV) has not been
shown to have a role in the management of this category of
hydrocephalus as the etiology is the absorption defect to a
large extent. ETV could be considered as an alternative to avoid
EVD‑associated infection. ETV is likely to help in managing
raised ICP. Till complete clearance of intraventricular and
subarachnoid bleed, ETV can be considered as a temporary
intervention in certain conditions. [37] Figure 2 gives an
algorithm‑based treatment strategy of hydrocephalus in the
setting of subarachnoid hemorrhage.
Conclusion
Hydrocephalus in SAH is infrequently seen in any
neurosurgical setup. The risk factors include higher
clinical and radiological grade, comorbidity, advanced
age, intraventricular bleed, and A.Com complex aneurysm.
Diagnosis is by a simple plain CT scan of the brain.
Management is watchful, closed temporary drainage system,
or a permanent CSF diversion with VP shunt. It occurs
with both groups of treatment, whether clipping or coiling.
Fenestration of lamina terminalis during microscopic open
surgery does not have a bearing on the incidence, and ETV
has essentially no role in the treatment.
Figure 2: Algorithm of treatment for hydrocephalus in a setting of subarachnoid
hemorrhage. X: when external ventricular drain does not work
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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 Review Article

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Quick Response Code:
Idiopathic Intracranial Hypertension
‑ Challenges and Pearls
Wadikhaye Rohit, Alugolu Rajesh1, Rukmini Mridula2, Shaik A Jabeen2

Website: Abstract:
www.neurologyindia.com
Idiopathic intracranial hypertension (IIH) is defined as a syndrome of raised intracranial pressure with normal
DOI: imaging of the brain and cerebrospinal fluid (CSF) composition. There is a rising incidence and prevalence
10.4103/0028-3886.332276 of this disease related to the increased prevalence of obesity. It typically affects women of working age, and
headache is the predominant morbidity in over 90%. The disease is also more prevalent in young males.
There are many controversies and myths that surround IIH. There are currently few treatment options for
IIH, management is typically medical with those experiencing progressive visual loss undergoing surgical
procedures. Weight loss and venous sinus stenting are a few therapies directed at the etiology.
Key Words:
Cerebrospinal fluid, headache, idiopathic intracranial hypertension, optic nerve sheath fenestration,
papilledema, pseudotumor cerebri, raised intracranial pressure

Key Message:
IIH is a disorder of unknown etiology with many hypothesis, the treatment of which should be individualized
to protect the vision and reduce the morbidity caused by headache and other symptoms.

I diopathic intracranial hypertension (IIH),

also known as pseudotumorcerebri (PTC),
is characterized by increased intracranial
“benign” in the description was challenged in
1969 by Buchheit et al.[7]

pressure (ICP), commonly seen in young, IIH was used by Corbett and Thompson in the
obese women, manifested commonly by late 1980s.[8]
headaches and visual symptoms. The syndrome
of IIH was first recognized by Quincke and Epidemiology
later by Nonne.[1,2] The disease with no clear
cause has many hypotheses, nomenclature, IIH is a rare condition with an incidence of 0.2–2
disease manifestations, treatment options per 100,000 in the general population between
including medical, surgical, and behavior 25 and 36 years, more common in women
modifications. (7.7 vs. 1.6 per 100,000).[9‑13] However, this gender
bias is not seen in adolescents. A 118% increase
RVM Institute of History and Nomenclature in the incidence of IIH in females has been seen
Medical Science and from 2002 to 2016.[10]
Research Centre, The first description of a case of   pseudotumor
Departments of cerebri syndrome (PTCS) was by Bouchat Classification
1
Neurosurgery and in 1866 (reported by Passot, 1913) and was
2
Neurology, Nizam’s termed meningeal hypertension.[3] Quincke (1897)
IIH is divided into primary and secondary
Institute of Medical called it serous meningitis. Taylor (1890) was
the first to describe patients with increased based on the etiology [Table 1].[14] The primary
Sciences, Hyderabad,
Telangana, India ICP with a normal CSF in the absence of PTC and primary IIH are synonymous. If we
a tumor. [1,4] Dandy  (1937) coined the term use the term IIH without any prefix, it means
Address for ‘intracranial pressure without brain tumor’.[5] primary IIH. Another way is to use the term
correspondence: Later “benign intracranial hypertension” was pseudotumor cerebri which is further subdivided
Dr. Alugolu Rajesh, suggested by Foley in 1955.[6] The inclusion of as definite, probable [Table 2].
Department of
Neurosurgery, Department
of Neurosurgery, Nizam’s How to cite this article: Rohit W, Rajesh A,
Institute of Medical This is an open access journal, and articles are distributed under the terms Mridula R, Jabeen SA. Idiopathic Intracranial
Sciences, Punjagutta, of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 Hypertension - Challenges and Pearls. Neurol India
Hyderabad ‑ 500 082, License, which allows others to remix, tweak, and build upon the work
2021;69:S434-42.
Telangana, India. non‑commercially, as long as appropriate credit is given and the new
creations are licensed under the identical terms. Submitted: 09‑Jul‑2021 Revised: 22-Sep-2021
E‑mail: drarajesh1306@
Accepted: 25‑Sep‑2021 Published: 11-Dec-2021
gmail.com For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com

S434 © 2021 Neurology India, Neurological Society of India | Published by Wolters Kluwer - Medknow
 Rohit, et al.: IIH ‑ Challenges and pearls

Diagnostic Criteria for IIH morbidity from headaches, but their vision is no longer at risk
while there is no papilledema.[17]
Modified Dandy criteria, updated by Friedman in 2002 and
2013, are advocated for the diagnosis of IIH [Table 2]. IIH with spontaneous CSF leak
Diagnosing and managing IIH in the setting of a CSF leak poses
Other Variants specific challenges because the symptoms and signs of raised
ICP are absent as the CSF leak acts as a fistula.[18,19]
Fulminant IIH
The criteria needed are COVID‑19 and IIH
a) Diagnostic criteria for IIH including papilledema The corona virus disease of 2019 (COVID-19) infection has been
b) Less than 4 weeks between symptom onset and severe loss associated with new‑onset IIH as well as secondary causes of
of visual acuity or field intracranial hypertension. In a series of 56 patients with COVID‑19
c) Rapid worsening of vision over days.[15] who underwent lumbar puncture, 23.2% had a new‑onset
headache, and among them, six patients  (46.1%) fulfilled the
IIH without Papilledema (IIHWOP) criteria for IIH.[20] Cerebral sinovenous thrombosis CSVT and
multisystem inflammatory syndrome are the most common
The clinical characteristics remain similar except that the secondary causes of intracranial hypertension in COVID‑19.[21]
mean CSF opening pressure is lower with a decreased threat
to vision [Table 2].[16] Challenges in Pathogenesis

Atypical IIH The pathogenic mechanisms of IIH are still unclear.

Patients meeting the diagnostic criteria of IIH but (i) male
gender, (ii) not in childbearing age, and (iii) body mass index
(BMI) below 30 kg/m2.[17]
IIH in ocular remission
Patients who have been diagnosed with IIH and the
papilledema has resolved. These patients may have ongoing
Multiple mechanisms have been suggested to explain the
pathophysiology of IIH [Figure 1].
Increased cerebral volume or cerebral blood volume
A role of increase in the cerebral volume secondary to white
matter edema or increase in the cerebral blood volume has
been postulated, but with no evidence.

Table  1: Classification of IIH CSF dysregulation

A. Primary idiopathic intracranial hypertension Currently, the main pathogenic mechanism revolves around
Includes patients with obesity, recent weight gain, polycystic ovarian dysregulated CSF dynamics.[22] The CSF is secreted by the choroid
syndrome, and thin children plexus, and regulated by the enzyme Na+ K+ ATPase.[23] The role
B. Idiopathic intracranial hypertension of aquaporin, a water transporting channel in the pathogenesis
Cerebral venous abnormalities
of IIH, is unclear except for the aquaporin 1 channel.[24]
Cerebral venous sinus thrombosis
CSF outflow obstruction
Bilateral jugular vein thrombosis or surgical ligation
CSF drains from the subarachnoid space through arachnoid
Middle ear or mastoid infection
granulations into the superior sagittal sinus. A part of CSF
Increased right heart pressure drainage happens through the cranial nerves and cribriform
Superior vena cava syndrome plate into the lymphatics into the deep cervical lymph nodes.[25]
Arteriovenous fistulas
Decreased CSF absorption from previous intracranial infection or
subarachnoid hemorrhage
Hypercoagulable states
Medications and exposures
Antibiotics-Tetracycline, minocycline, doxycycline, nalidixic acid,
sulfa drugs
Vitamin A and retinoids-Hypervitaminosis A, isotretinoin, all‑trans
retinoic acid for promyelocytic leukemia, excessive liver ingestion
Hormones-Human growth hormone, thyroxine (in children), leuprorelin
acetate, levonorgestrel (Norplant system), anabolic steroids
Withdrawal from chronic corticosteroids
Lithium
Chlordecone
Medical conditions
Endocrine disorders-Addison disease, Hypoparathyroidism
Hypercapnia-Sleep apnea, Pickwickian syndrome
Anemia
Renal failure
Turner syndrome
Down syndrome Figure 1: Pathophysiology of IIH
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S435
 Rohit, et al.: IIH ‑ Challenges and pearls
A new “glymphatic pathway” is identified wherein there is an
exchange of fluid between the CSF and the interstitial fluid along
the perivascular routes.[26] However, there is no direct evidence
of dysfunction of the arachnoid villi and granulations in IIH.[27]
Intracranial venous hypertension
One of the causes of IIH is the bilateral stenosis of the distal
portion of the transverse cerebral sinuses which results in
reduced absorption of CSF via the arachnoid granulations. It is,
however, not clear whether this stenosis is incidental, primary,
or secondary to increased ICP.[28]
Any cause of increased intracranial pressure can cause
compression of the transverse sinus, which can lead to further
elevated ICP, which in turn leads to further stenosis, resulting
in a positive feedback loop.[29]
Neurometabolic defects
It is suggested that the mitochondria in the perivascular
astrocytes endfeet and neurons of IIH patients are pathological,
resulting in an impaired metabolism at the neuro-glio-vascular
interface and maybe a facet of IIH.[25]
Risk factors and the risk of IIH
Obesity
Central body fat causes
1. Increase in central venous pressure and increase venous
pressure, reducing CSF absorption.[30]
2. Prethrombotic state and microthrombi in cerebral sinuses
result in intracranial venous hypertension.[31]
3. Increasing leptin and reducing incretin lead to CSF
hypersecretion.[32]
4. Dysregulation of 11 beta‑hydroxysteroid dehydrogenase‑1
enzyme (11β‑HSD1) causes increased CSF cortisol and
stimulation of mineralocorticoid receptors leading to
increased CSF secretion.[33]
Female gender
Women with IIH have been found to have a unique circulating
androgen excess signature, with significantly higher active
testosterone but lower concentrations of the androgen
precursors dehydroepiandrosterone sulfate (DHEA) and
androstenedione.[34]
Clinical Features
The symptoms and signs of IIH should be attributable to raised
CSF pressure.
Headache
Headache is the commonest symptom causing major disability
in 90% of the patients.[35] IIH headache may vary from throbbing,
pressing, and explosive and is frontal in location. In the idiopathic
intracranial hypertension treatment trial (IIHTT), headache was
described as migrainous in 52%, tension‑type in 22%, probable
migrainous or tension‑type in 16 and 4%, respectively.[36] The
diagnostic criteria in International Classification of Headache
Disorders (ICHD)‑3 [Table 3] emphasize the need for the
presence of associated symptoms and signs for diagnosis.[37] The
absence of headache can be seen in a small subset of patients
and can portend a worse visual prognosis.[38]
S436 Neurology India | Volume 69 | Supplement 2 | November-December 2021
Table  2: Modified Dandy criteria
Diagnostic criteria for pseudotumor cerebri syndrome
1. Required for diagnosis of pseudotumor cerebri syndrome
A. Papilledema
B. Normal neurologic examination except for cranial nerve
abnormalities
C. Neuroimaging: Normal brain parenchyma without evidence
of hydrocephalus, mass, or structural lesion and no
abnormal meningeal enhancement on MRI, with and
without gadolinium, for typical patients (female and obese),
and MRI, with and without gadolinium, and magnetic
resonance venography for others; if MRI is unavailable or
contraindicated, contrast‑enhanced CT may be used
D. Normal CSF composition
E. Elevated lumbar puncture opening pressure (≥250
mm CSF in adults and ≥280 mm CSF in children [250
mm CSF if the child is not sedated and not obese]) in a
properly performed lumbar puncture
Definite PTCS: if criteria A‑E are fulfilled.
Probable PTCS: if criteria A‑D are met with bilateral papilledema
present, and the measured CSF pressure is lower than specified for
a definite diagnosis.
2. Diagnosis of pseudotumor cerebri syndrome without
papilledema/IIHWOP
In the absence of papilledema, a diagnosis of pseudotumor cerebri
syndrome can be made if B‑E from above are satisfied, and in
addition, the patient has a unilateral or bilateral abducens nerve palsy
In the absence of papilledema or sixth nerve palsy, a diagnosis of
pseudotumor cerebri syndrome can be suggested but not made if
B‑E from above are satisfied, and in addition, at least three of the
following neuroimaging criteria are satisfied:
a. Empty sella
b. Flattening of the posterior aspect of the globe
c. Distention of the perioptic subarachnoid space with or
without a tortuous optic nerve
d. Transverse venous sinus stenosis
Table  3: Diagnostic criteria for IIH‑related headache
according to the International Classification of
Headache Disorders  (ICHD‑3)
A New headache, or a significant worsening of a pre‑existing
headache, fulfilling criterion C
B Both of the following:
1 idiopathic intracranial hypertension (IIH) has been diagnosed
2 cerebrospinal fluid (CSF) pressure exceeds 250 mm CSF (or
280 mm CSF in obese children)
C Either or both of the following:
1 headache has developed or significantly worsened in
temporal relation to the IIH, or led to its discovery
2 headache is accompanied by either or both of the following:
a) pulsatile tinnitus
b) papilledema
D Not better accounted for by another ICHD‑3 diagnosis
Visual disturbances
Transitory visual obscurations (TVO) varying from slight
blurring to total loss of light perception is seen in up to 60–72%
of the patients of IIH.[39] TVO are usually bilateral, lasting
less than a minute, several times a day, and are provoked
by postural changes and Valsalva maneuver. Other visual
abnormalities include loss of color vision and peripheral
 Rohit, et al.: IIH ‑ Challenges and pearls
vision. Acute vision loss can happen in some patients, usually
associated with headache. Fulminant IIH can portend a serious
risk of permanent vision loss unless treated immediately.
Pulsatile Tinnitus
Pulsatile bruit‑like tinnitus, unilateral or bilateral due to
turbulence in the jugular vein occurs in approximately 52–61%
of the patients and resolves with the normalization of CSF
pressure.[40] Non‑pulsatile tinnitus has also been seen in 23%
of the patients.[41]
Diplopia
Horizontal diplopia secondary to raised ICP causing unilateral
or bilateral sixth nerve palsies is seen in 10–20% of the patients.[39]
Other symptoms frequently seen are back pain (53%),
dizziness (52%), neck pain (42%), cognitive disturbances (20%),
and radicular pain (18.2%).[41]
Rare Presentations
Other cranial nerve palsies
Third, fourth, or seventh cranial nerve palsies can occur as false
localizing signs of raised ICP.[42‑45] Olfactory dysfunction can
happen due to the compression of the olfactory nerve over the
cribriform plate or alterations in the lymphatic drainage around
the nasal mucosa. Hearing loss of variable degree has been
reported which improves with a reduction in CSF pressures.[46]
Rarely trigeminal nerve dysfunction can occur as a result of
raised ICP or CSF leak and meningocele formation.
Seizures
A retrospective assessment of 22 patients with temporal
lobe‑onset seizures due to anteroinferior temporal
meningoencephaloceles showed magnetic resonance imaging
(MRI) findings suggestive of IIH in one‑third.[42, 47]
Papilledema [Figure 2] Raised CSF pressure is transmitted to
the optic nerve causing raised perineural pressure causing stasis
of retinal veins and stoppage of axoplasmic transportation.
Figure 2: Fully developed papilledema
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S437
Papilledema may be asymmetric with a difference of two or
more Frisen grades in up to 10% of the cases. Optical coherence
tomography (OCT), is a more sensitive investigation, useful for
quantified monitoring of the optic nerve head swelling during
patient follow‑up. OCT measures are reliable for diagnosing
subtle IIH even in the absence of papilledema.[48]
Visual field defects appear in up to 96% of the patients during
the course of IIH.[49] The enlargement of blind spot is the most
frequent and the earliest visual field defect in IIH and is often
an inferior nasal step defect followed by peripheral nasal loss;
arcuate defects may appear next.[50] Central defects are distinctly
uncommon and warrant a search for another diagnosis unless
there is a large serous retinal detachment [Figure 3].[51]
IIHWOP patients does not have any visual field defects.
However, they can have functional or non‑physiological visual
defects which persist even after therapy.[52]
Visual acuity remains normal initially. The impairment of
visual acuity is an ominous sign and is due to nerve fiber
atrophy, choroidal folds, macula edema or exudates, nerve disk
infarct, or subretinal peripapillary hemorrhages.[53]
Acute visual loss, seen in a small subset of patients, develops
due to a sudden increase in the ICP causing a vascular
compromise in the optic nerve head causing massive
papilledema and peripapillary retinal hemorrhages.
Investigations
The objectives in the investigation of IIH are
1. To establish the existence of raised ICP
2. Evaluate severity
3. Exclude other causes of raised ICP
4. Identify etiological factors responsible for the IIH.
CSF Pressure
Conventionally, the upper limit of the normal CSF opening
pressure is defined as 200 mm H2O measured with the patient in
lateral decubitus position with legs extended and as relaxed as
possible. Corbett and Mehta have reported pressures between
200 and 250 mm H2O in both obese (25%) and non‑obese (7%)
healthy individuals.[54] Children have higher opening pressures
and the cut‑off value is given as 280 mm H2O.[55] The opening
pressure does not always give the true steady‑state pressure
due to natural fluctuations. Anxiety and hyperventilation can
lower pressures resulting in a false‑negative test.
a b
Figure 3: Common types of visual field abnormalities: (a) Enlarged blind spot
(b) Superior and inferior arcuate defects
 Rohit, et al.: IIH ‑ Challenges and pearls

Neuroimaging insufficient evidence to recommend or reject the efficacy of

this intervention.[61]
MRI and MRV Brain
MR venogram (MRV) is done routinely to rule out transverse Topiramate—a weak carbonic anhydrase inhibitor as a
sinus thrombosis. In patients with no evidence of venous sinus substitute for acetazolamide has been found to have better
thrombosis, signs of elevated CSF pressure on MRI [Table 4, efficacy in lowering ICP as compared to acetazolamide.[62] It
Figure 4a and b] can help in the diagnosis of IIH.[56] may cause a cognitive slowing in a subset of patients and has
teratogenic effects.
Challenges in Treatment
Alternative drugs which may be prescribed are furosemide,
The aim of treatment is to reduce ICP, relieve headache, and amiloride, and octreotide.
preserve vision. The treatment can thus be grouped as.
11b‑hydroxysteroid dehydrogenase type 1 inhibitor
Modifying the Underlying Disease (AZD4017) ‑ The enzyme 11b‑hydroxysteroid dehydrogenase
type 1 has been implicated in regulating cerebrospinal fluid
Weight loss is currently the only established disease‑modifying secretion. In a phase II RCT, AZD4017 was found to have a
therapy and is notoriously difficult to achieve and maintain. significant reduction in ICP.[63]
Weight loss of 15% in IIH significantly reduces papilledema
and headache.[57] Headache treatment in IIH with resolved papilledema:
Erunumab—a monoclonal antibody against calcitonin gene‑related
Glucagon‑like peptide 1 (GLP‑1) receptor agonist acts on the peptide has been tried with benefit in this subset of patients.[64]
hypothalamus to reduce food intake and on the adipose tissue
to increase lipolysis resulting in weight loss.[58] Also, the choroid Surgical Treatment
plexus has been found to express GLP‑1 receptors, and treatment
with a GLP‑1 RA significantly reduces cerebrospinal fluid Surgical interventions are recommended for medically refractory
secretion, and thus, can become a potential treatment for IIH.[59] and fulminant IIH. There are no established evidence‑based
guidelines regarding the surgical treatment options for IIH.[65]
Medical Therapy
Surgery to Treat the Etiology
Acetazolamide is a carbonic anhydrase inhibitor that is
thought to reduce CSF production by the choroid plexus. These procedures treat the etiology and provide long‑term
Acetazolamide is safe and generally well‑tolerated up to 4 g/ remission of the disease.
day. It, however, has no benefit on headache severity.[60] The 1. Bariatric surgery ‑ In patients without optic nerve
current Cochrane review on IIH management included two injury, weight loss intervention can be considered as
randomised controlled trial (RCTs) which showed modest a monotherapy, but close ophthalmic monitoring is
benefits for acetazolamide for some outcomes but showed imperative due to the high chances of treatment failure
and complications up to 55%.[66,67] A randomized study of
the surgical and non‑surgical approaches to weight loss for
IIH treatment is in process.[68]
2. Venous Sinus Stenting ‑ Cerebral venous sinus stenting
aims to reduce cerebral venous hypertension by opening
stenosis in one of the transverse sinuses. This appears to
be safe and effective in the short term in carefully selected
patients.[69] A recent review of the surgical treatment methods
in IIH suggests that venous sinus stenting (VSS) is the most
a b efficient surgical intervention in regard to visual outcomes,
with 87.1, 72.7, and 64.6% of the patients improving with
Figure 4: Common MRI features: (a) Empty sella, (b) Posterior flattening of the
globe respect to papilledema, visual fields, and visual acuity,
respectively, and 78–83% improvement in headache.[70] The
complications can be an ipsilateral headache, stent‑adjacent
Table  4: MRI/MRV Findings in patients with IIH stenosis, stent migration, and thrombosis.[70] Among the
Findings Specificity Incidence Sensitivity Specificity serious complications arising from VSS, an instance of
Partially empty sella 76‑85% 80‑88% 76‑92% bilateral cerebellar hematoma, obstructive hydrocephalus,
Distension of peri‑optic 95% 72‑80% 96% and death are reported.[71]
subarachnoid space
Flattening of posterior globe 43‑71% 28‑43% 100% Surgery for Palliation: Aimed to Save the Vision
Optic nerve protrusion 3‑71% 3% 100% Primarily and not Addressing the Reason for Raised
Tortuous optic nerve 40‑62% 40% 91% ICP
Transverse sinus stenosis 65‑95% 93% 93%
Enlarged Meckel’s cave or 9 or 11% NA NA 1. Subtemporal decompression – Introduced in the late
Meningocele nineteenth century by Horsley and others for controlling

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 Rohit, et al.: IIH ‑ Challenges and pearls
intracranial hypertension, it has in the past occupied a
significant place in the therapeutic armamentarium against
IIH.[72]
2. CSF diversion procedures including ventriculo‑peritoneal,
lumbo‑peritoneal, and less frequently, ventriculo‑atrial
shunting may be utilized. Ventriculo‑peritoneal shunts
are preferred due to lower revision rates compared to
lumbo‑peritoneal shunts (1.8 vs. 4.3 revisions per patient,
respectively).[65] The severe complication rate in the CSF
shunt procedures is 9.4% with the most common severe
complication being shunt infection.[73] Most of the revisions
are carried out due to shunt obstruction.[74]
Post‑LP headache exacerbation is common up to 64% and
in some prolonged and severe.[75]
3. Optic nerve sheath fenestration (ONSF) entails the
creation of a window in the optic nerve sheath, permitting
egress of CSF from the perineural subarachnoid space and
decreasing the pressure of CSF exerted on the optic nerve.
The approach for ONSF can be either transconjunctival,
endoscopic endonasal, or transcranial.
In the transconjunctival approach, visual acuity improved
in 67–71%, and visual fields showed improvement in 64%,
and disk swelling improved in 95% of the patients.[76] The
complication rates may vary from 4.8 to 45%.[77]
ONSF, through endoscopic approach, shows improvement
in the visual fields (VF) deficits (93.8%), VA (85.3%),
papilledema (81.4%), and headaches (81.8%) with no
complication described in a study by Tarrats et al.[78] The
complications can be CSF leak, meningitis, epistaxis, and
subcutaneous orbital emphysema.[79]
Transcranial ONSF using bone ultrasonic aspirator can achieve
a maximum 270° bony decompression and is found to be
more effective with a 90.47% improvement in VA, 80.95%
improvement in VF, and 66.67% relief in headache with reduced
complications than the conventional high‑speed drill.[80]
Unilateral subtemporal decompression with bilateral ONSF
has also been advocated in failed lumbar drain with persistent
symptoms.[81] ONSF has the lowest failure rate among the
surgical interventions with merely 9.4% of the patients
relapsing after an initially successful intervention.[67]
IIH in Pediatric Patients
Pediatric IIH was considered a relatively rare condition
until 1992 when Lessell defined the disorder in pediatric
patients.[82] The annual incidence of symptomatic IIH in the
pediatric age from 3 to 15 years is 0.9 per 100,000.[83] Two
subtypes: pediatric type and adolescent type are described.[84]
There is no agreement for specific diagnostic criteria in the
pediatric IIH due to controversies about the diagnostic value
of CSF opening pressure.[85] IIH in pediatric patients usually
responds to pharmacological treatment with a low rate of
recurrence.
IIH in Pregnancy
During pregnancy, it generally appears in the first half
of gestation although IIH can appear in any trimester of
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S439
pregnancy and pregnancy does not alter the natural history
of the disease. Acetazolamide use is controversial due to
reports of teratogenic effects. The use of other diuretics is
usually not recommended during pregnancy because the
lowering of maternal blood volume can reduce placental
blood flow.[86]
Surgical treatment is reserved for patients with severe
progressive visual loss. The optic nerve sheath fenestration
option is a better approach, and as a shunt is technically difficult
in pregnant women due to the gravid uterus.[87] Gestation does
not worsen the prognosis of IIH, neither affects the perinatal
outcome. IIH is not considered an indication for an elective
cesarean delivery.[88]
Newer Trials
SIGHT ‑ The Neuro‑Ophthalmology Research Disease
Investigator Consortium (NORDIC) are currently planning
a randomized‑controlled surgical trial, SIGHT, which will
compare shunting with ONSF and acetazolamide.[89]
VISION ‑ Another multicenter randomized‑controlled trial,
the VISION study (Venous Intervention vs. Shunting in IIH
for Optic Disk Swelling) comparing the venous sinus stenting
to CSF shunting is being planned.[90]
Conclusion
IIH is a disease of varied etiologies, which apart from the
classical pattern in middle‑aged females, is now seen in
younger people across the gender. Diet and weight control
with medical management form the first line of treatment.
Neurosurgical procedures, apart from venous stenting, are
the basic rescue procedures undertaken to prevent visual
loss.
Challenges and Pearls
The fundus pictures and OCT can help in identifying and
following papilledema. Perimetry is a must to pick up early
visual abnormalities.
Lumbar puncture and CSF pressure are the gold standards for
IIH diagnosis, but pressures can fluctuate and false negatives
are common.
MRI brain is a sensitive tool for identifying IIH.
Early in disease behavior modification and weight loss with
or without pharmacotherapy.
Bariatric surgery for weight loss seems promising.
Shunts and optic nerve decompressions work on the principle
of a functioning fistula.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
 Rohit, et al.: IIH ‑ Challenges and pearls
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 Review Article

Access this article online

Quick Response Code:
Malignant Meningitis Associated with
Hydrocephalus
Ashutosh Kumar, Jayesh C Sardhara, Guramritpal Singh, Soumen Kanjilal,
Ved P Maurya, Sanjay Behari

Website:
www.neurologyindia.com
Abstract:
DOI: Malignant meningitis (MM) is the diffuse involvement of the leptomeninges by infiltrating cancer cells, most
10.4103/0028-3886.332278 frequently from lung and breast cancers. This review is aimed to discuss the current advances in the diagnosis
and management of MM, along with management of MM‑associated hydrocephalus. We reviewed the literature
using PubMed and Google Scholar search engines, focusing on various recent randomized controlled trials
and clinical trials on MM. Given the hallmark multifocal involvement, the clinical symptoms and signs are also
random and asymmetric. There are three important pillars for establishing a diagnosis of MM: clinical examination,
neuroimaging, and CSF cytological findings. Several factors should be considered in decision‑making, including
performance status, neurological findings (clinical, MRI, and CSF flow dynamic), and evaluation of the primary
tumor  (nature and systemic dissemination). Response Assessment in Neuro‑Oncology  (RANO) working
group recommended the objective assessment of disease for evaluating the progression and response to
therapy. Pillars of current management are mainly focal irradiation and intrathecal or systemic chemotherapy.
Symptomatic hydrocephalus is managed with a ventriculoperitoneal shunt, lumboperitoneal shunt, or endoscopic
third ventriculostomy as palliative procedures, providing significant improvement in performance scores in the
limited survival time of patients with MM. Studies using novel therapeutic approaches, such as new biological or
cytotoxic compounds, are ongoing. Despite the use of all the combinations, the overall prognosis remains grim;
therefore, decision‑making for treatment should predominantly be based on attaining an optimal quality of life.
Key Words:
Focal radiotherapy, intrathecal chemotherapy, leptomeningeal metastasis, malignant meningitis, metastasis
management, RANO

Key Message:
Therapeutic measures directed towards malignant meningitis aim to attain an optimum quality of life, rather
than trying to prolong survival.

M alignant meningitis (MM) is the involvement

Department of
Neurosurgery, Sanjay
Gandhi Postgraduate
Institute of Medical
Sciences, Lucknow,
Uttar Pradesh, India
Address for
correspondence:
Dr. Sanjay Behari,
Department of
Neurosurgery, Sanjay
Gandhi Postgraduate
Institute of Medical
Sciences, Lucknow,
Uttar Pradesh, India.
E‑mail: sbehari27@gmail.
com
of the leptomeninges (arachnoid and
pia mater) along with the subarachnoid
space by malignant cells originating from an
extra meningeal primary tumor site. It is also
known as “leptomeningeal carcinomatosis” or
“leptomeningeal metastasis” or “carcinomatosis
meningitis.” It was first described in the late
19th century.[1] MM is the third most common
metastatic complication affecting the central
nervous system, after brain and spinal epidural
metastasis.[2‑4] Once a patient is diagnosed with
MM, it is already a stage‑four disease. The
management goal in such a scenario is focused on
palliation and adding “life to months.” Recently,
there have been significant advances in the
diagnosis and management of MM. It includes
the RANO guidelines for preferred diagnosis
This is an open access journal, and articles are distributed under the terms
of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0
License, which allows others to remix, tweak, and build upon the work
non‑commercially, as long as appropriate credit is given and the new
creations are licensed under the identical terms.
For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com
and reporting of disease progression, agents, and
route for chemotherapy administration. With
the advancement in the molecular and genetic
understanding of primary malignancies, the
role of immunotherapy and targeted therapy
in MM is also being explored. Presently, it is
one of the fields with a limited understanding
of pathogenesis, diagnosis, and management
options, demanding extensive research.
Hydrocephalus is the most common complication
of MM and severely affects the performance
score of the patients. Yet, there exists no level
1 evidence for its management. This review
is aimed to discuss the current advances
in the diagnosis and management of MM,
along with the management of MM‑associated
How to cite this article: Kumar A, Sardhara JC,
Singh G, Kanjilal S, Maurya VP, Behari S. Malignant
Meningitis Associated with Hydrocephalus. Neurol
India 2021;69:S443-55.
Submitted: 13‑Jul‑2021 Revised: 27-Oct-2021
Accepted: 13-Sep-2021 Published: 11-Dec-2021

© 2021 Neurology India, Neurological Society of India | Published by Wolters Kluwer - Medknow S443
 Kumar, et al.: Malignant meningitis with hydrocephalus
hydrocephalus. We reviewed the literature using PubMed
and Google Scholar search engines with a particular focus on
recent randomized controlled trials and clinical trials on MM.
Epidemiology
The primary lesion can be a solid tumor or a hematologic
malignancy. “Carcinomatous meningitis” or “meningeal
carcinomatosis” are the alternative terms often used for MM
secondary to a systemic primary cancer. The primary solid
tumors can be systemic or intrinsic brain tumors. MM is reported
in 4%–15% of the systemic cancers.[5‑9] The most common sources
are malignancies from breast, lung, and melanoma in decreasing
order of frequency. The reported incidence of MM is highest in
melanomas (up to 30%). It is 9%–25% in lung cancers (higher
incidence in small‑cell lung cancer as compared to other
subtypes) and 5%–8% in breast cancers.[10‑12] At the diagnosis,
MM can present with brain metastasis (33%–75%), concurrent
involvement of dura (16%–37%) or it may be the first site of the
metastasis (20%).[7,13‑17] Further, 60%–70% of patients present with
progressive primary systemic disease.[7,9] The overall incidence
of MM is rising due to progressively better systemic control of
the primary tumor, which has improved survival, and due to
the performance of Gd‑enhanced MRI of the whole neuraxis,
which allows for the detection of even tiny lesions. As most
chemotherapeutic agents cannot cross the blood–brain barrier, the
subarachnoid space acts as a “sanctuary site” for leptomeningeal
metastasis (LM). While the systemic disease is addressed, it is
not rare to find isolated MM.[18‑20] Symptomatic hydrocephalus
was reported in 25.4% of patients (n = 71) of MM by Jung et al.[21]
The primary brain tumors that can present with MM
include glioblastoma multiforme, medulloblastoma, and
ependymoma [Figure 1]. MM due to a hematological
malignancy includes that due to lymphomatous or leukemic
meningitis, reported in 5%–15% of patients with lymphoma
or leukemia. [3,22] Other rare sources of metastasis to the
leptomeninges include prostate tumors, head and neck
tumors, squamous cell carcinoma, thyroid cancer, rectal cancer,
carcinoid tumors, and rhabdomyosarcoma.
a b
Figure 1: An operated case of fourth ventricular medulloblastoma (a) presented with drop metastasis involving the lumbar thecal sac (b) and the cervical cord (c) after
6 months following resection
S444 Neurology India | Volume 69 | Supplement 2 | November-December 2021
Pathogenesis and dissemination of MM
Though the underlying pathogenesis of MM is still not
well understood, Boyle et al., reported the possible role of
complement factor 3 (C3) in the mechanism of invasion
and colonization of malignant cells within the CSF and
leptomeninges. They postulated that once the malignant cells
extend to the leptomeninges, they upregulate the production of
C3. This disrupts the BBB and allows various growth factors to
enter the CSF. Vascular endothelial growth factor (VEGF) was
implicated as the most important among them.[23] It promotes
malignant cell proliferation and angiogenesis.
The cells migrate to different parts of the CNS with the CSF
or extend along the meninges. This leads to a multifocal CNS
involvement, a hallmark of MM. It explains why basal cisterns,
posterior fossa, and cauda equina (lumbar thecal sac) are the
most common sites.[23] The hematological malignancies cause
a diffuse involvement. The solid tumors mostly present with
plaque‑like or nodular deposits along the leptomeninges.
As the metastatic cell deposits grow, they may invade the
subpial brain parenchyma, compress the spinal cord/nerve
root, or they may involve the dura mater. The involvement of
dura gives a strategic benefit in management with systemic
chemotherapy as it is not protected by the BBB.
The invasion of leptomeninges by the metastatic cells can occur
by hematogenous spread, direct extension from the adjacent
structures (brain parenchyma/dura), and spread along the
endoneurial/perineural or perivascular lymphatics. Among
all, the hematogenous route is the most common, more so
for the hematological malignancies than for the solid tumors.
The vertebral and para‑vertebral metastasis are proposed
to be because of perineural/endoneurial spread along the
peripheral nerves, while in the case of prostate cancer, the
retrograde spread of tumor cells along the valveless Batson’s
plexus is postulated as the possible route.[24‑27] During invasive
neurosurgical procedures, as the ependyma or the dura is
breeched, the tumor cells can invade the tract formed by the
surgical trajectory. This is a rare cause of iatrogenic spread
causing MM.[28‑30]
c
 Kumar, et al.: Malignant meningitis with hydrocephalus
Clinical presentation
The clinical manifestations depend upon the location of the
neuraxis involved. Given the hallmark multifocal involvement,
the clinical symptoms and signs are also random and asymmetric.
Many times, the neurological manifestations are nonspecific,
requiring a high index of suspicion for establishing the diagnosis.
Cerebral involvement presents with headaches, seizures,
alteration of sensorium, or amnesia. Multiple cranial nerves are
often involved. Most commonly, VI, VII, and VIII nerves are
affected. Few studies reported III nerve as the most common
cranial nerve deficit. Hydrocephalus is the most common
complication of malignant meningitis. Deposition of metastatic
cells at the skull and base blocks the arachnoid villi, causing
impaired CSF absorption and communicating hydrocephalus.
Direct occlusion of the CSF pathway or the outflow foramina
by the tumor cells can also present with acute obstructive
hydrocephalus, though the latter is less common than the
communicating type. The development of hydrocephalus causes
significant morbidity in the limited survival time of patients with
malignant meningitis because of symptoms of severe headache,
ataxia, cognitive impairment, and urinary incontinence. Despite
appearing as communicating hydrocephalus, multiple adhesions
in the subarachnoid space may obstruct the free flow of CSF and
may precipitate hydrocephalus. Patients can also develop raised
intracranial pressure when the deposits are along the superior
sagittal sinus and compress it.[31] Alteration in circulation due
to direct compression or vasospasm of cortical vessels over the
convexities can lead to focal ischemic events.[32] Similarly, local
metabolic derangements can cause diffuse encephalopathy in
patients with extensive MM.[33]
Deposition along the spinal cord can present with myelopathy,
with or without radiculopathy, or with radiculopathy alone.
Cauda equina syndrome can be a presenting complaint when
the lumbar thecal sac is involved.
Diagnosis
There are three important pillars for establishing a diagnosis of
MM: clinical examination, neuroimaging, and CSF cytological
findings. As most patients present with an advanced primary
systemic disease and the signs and symptoms of MM are subtle,
random, and nonspecific, a high level of suspicion is crucial
for the diagnosis.
Clinical examination
The diagnosis begins with the identification of clinical features
of involvement of CNS anatomical substrates. A detailed
neurological assessment is essential as multifocal involvement
is a key feature of MM. In most cases, brain and dural metastasis
are present along with MM. Their symptoms are more
dominant, while those because of MM may remain obscured.
In less than 15% of cases, signs of meningeal irritation, such as
Kerning’s sign or Brudzinski’s signs, can be elicited.
Neuroimaging
On clinical suspicion of MM, the next step to diagnosis is
radiological imaging of the whole neuraxis. Gadolinium‑enhanced
MRI continues to be the investigation of choice despite the
emergence of major new imaging sequences.[34,35] The metastatic
cells are seen as enhancement along the leptomeningeal layer,
ependymal layer, and nerve sheaths in a linear or nodular pattern.
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S445
Often, the deposit may be visible as only an irregularity in the
ventricular lining or the dura [Figure 1].[13,14,16] Communicating
hydrocephalus may be noted as an associated finding.
False‑positive MRI features are noted in infectious meningitis,
post lumbar puncture, post‑intra‑thecal chemotherapy,
sarcoidosis, and post‑surgery. More importantly, it can be false
negative in 30%–70% of cases. Thus, MM cannot be ruled out
only based on a negative MRI. MRI has a greater sensitivity and
specificity for solid tumor‑associated MM than hematological
malignancy, as the former has more bulky lesions.[14,36,37]
The only other indication of neuro‑imaging in MM at present is to
assess the CSF flow dynamics before administration of intrathecal
chemotherapy.[38‑40] Tumor‑induced aberration in CSF flow
prevents the even distribution of the drug. This may prevent it
from reaching the target site or an abnormal accumulation at one
place can lead to neuro‑toxicity. Time‑resolved 2D phase‑contrast
MRI with velocity encoding is the most common MRI technique
to assess the CSF flow. Apart from this, radionuclide studies
employing 111‑(diethyl triamine pentaacetic acid (DTPA),
11‑indium, or 99‑technetium can also be performed.
CSF cytology/Flow cytometry
There is almost always some abnormality detected in CSF
studies in MM.[7,8,17,41,42] The opening pressure is elevated in up
to 50%–70% of cases.[43] Hypoglycorrhachia (<40 mg/dl) and
elevated protein levels are present in 25%–40% and 80% of the
cases, respectively. False‑negative cytology can be seen in up to
50% of the cases.[17,44] A repeat CSF cytology is recommended
as the sensitivity after second and third sampling improves
to 85%–90%.[7,17] The diagnostic yield can be further improved
by taking adequate sample volume (>10 mL), immediate
processing (no refrigeration), choosing the sampling site
nearest to the lesion and CSF sample collection from the lumbar
thecal sac as against ventricular fluid.[17,37,45] Malani et al.[46]
recently reported that the CSF circulating tumor cells (CTCs)
were more accurate than CSF cytology for establishing the
diagnosis, as well as for serving as a biomarker of treatment
response for MM from HER2+ breast cancers.
In MM secondary to hematological malignancy, flow cytometry
is performed along with cytology.[47,48] It has a high sensitivity
and can detect even 0.1% of the total CSF cell count.[49] Infections
and other inflammatory conditions should be ruled out as they
result in false‑positive cytology and flow cytometry results
in MM. Few studies have assessed the role of tumor markers
in CSF for establishing the diagnosis of MM. However, their
role has been mostly in supporting the diagnosis rather than
in being a diagnostic criterion.
Objective assessment of disease for progression and response
to therapy – RANO working group recommendations
To standardize reporting of the disease status, the Response
Assessment in Neuro‑Oncology (RANO) working group
proposed the objective criteria for the evaluation of MM.
Neurological assessment, neuroimaging, and CSF examination
remain the key elements of the proposed instrument.[50]
The neurological assessment included eleven domains
representing higher mental function (behavior, conscious
status), sensory‑motor functions (strength, sensation, and
gait), cranial nerves (II, III, IV, VI, VII, VIII, IX, X, and XI), and
 Kumar, et al.: Malignant meningitis with hydrocephalus
any other significant deficit. Each domain was scored from
0 (representing normal) to 3 (complete impairment). Three
domains, namely sensation, swallowing, and behavior, were
scored from 0 to 2. A disease was labeled as ‘progressive’ if there
was a change of score by 2 within a domain, or if the score was
changed to the highest score (3 or 2) of the domain.
The panel recommended volumetric 3DT1 (magnetization
prepared rapid acquisition with gradient echo or spoiled
gradient postcontrast images with isotropic 1‑mm voxels to
permit reformatting in three planes) MRI sequence for the initial
diagnosis and progressive assessment of the lesion. The cranial
and spinal lesions were evaluated separately, with a total of ten
elements to report. Leptomeningeal enhancement, nerve sheath
enhancement (cranial/nerve root), nodule, and parenchymal
metastasis were common elements in both categories. The fifth
element was hydrocephalus in the cranial, and epidural metastasis
in the spinal category. Both these elements and the parenchymal
metastasis were excluded from the MM response determination.
Each included element was reported as being present, absent, or
not‑evaluable at diagnosis. Lesions ≥ 5 × 10 mm in orthogonal
diameter were defined as measurable. All other lesions were
called unmeasurable. The overall radiographic score was
composite of the sum of the scores of both the types.
To make a CSF cytology report objective, the RANO working
group recommended reporting it as a binary outcome. It is
reported positive if the cytology report is positive or suspicious,
and reported negative if the report is negative or atypical. For
hematological malignancy‑associated MM, both CSF cytology
and flow cytometry were recommended to be used in parallel.
A response was defined as conversion from positive to negative
from the previous positive sites and maintaining the status for
4 weeks. Progressive disease was defined as either conversion
of negative to positive CSF cytology, or failure to convert
positive to negative CSF cytology following the induction a
phase (refractory disease).
There are certain limitations to this recommendation. The
assessment of MM may not be comprehensive due to the inherent
limitations of the diagnostic elements, such as low sensitivity
of the CSF cytology, the limitations in the ability of MRI for
performing a volumetric analysis of the lesions, and the subjective
nature of the clinical examination. Patient‑reported outcomes and
quality‑of‑life measures, which have a prognostic significance,
were acknowledged but not included in the scoring system.
Though these recommendations are a step toward standardization
of reporting of MM to allow for a comparison between studies, a
validation study by Rhun et al.,[51] expressed critical limitations
and proposed a new scorecard for the MM response assessment.
Nevertheless, it also needs further validation.
Management
Despite the poor prognosis, an early diagnosis and treatment
of MM allows for a longer duration of progression or the
development of fixed neurological deficits and possibly
improves overall survival. The treatment goal is palliative
and the prevention of significant morbidity secondary to MM.
It includes pain relief, alleviation of compression, and relief
from hydrocephalus. Though there is no defined treatment
regimen to date, a multimodality treatment comprising surgery,
radiotherapy, chemotherapy (systemic; intrathecal), and targeted
S446 Neurology India | Volume 69 | Supplement 2 | November-December 2021
therapy are employed based on the clinical scenario and the
primary tumor type.[52] Table 1 summarizes recent clinical trials
and randomized control trials related to the management of MM
associated with various primary malignancies.[46,53‑65]
Pain management
Pain due to meningeal irritation or infiltration of nearby
structures is managed with nonsteroidal anti‑inflammatory
drugs and opioids. Often, a combination of both these
medications is prescribed. Headache associated with raised
intracranial pressure because of cerebral edema is alleviated
by systemic steroids to some extent. The involvement of
nerve roots causes radicular pain. It is managed with calcium
channel α2δ ligands (pregabalin and gabapentin) and tricyclic
antidepressants (amitriptyline and nortriptyline). Less commonly,
Na channel blocking anti‑epileptic drugs (carbamazepine,
phenytoin, and lamotrigine) and serotonin–noradrenaline
reuptake inhibitors (SNRI) are also used. Focal radiotherapy
can be effective in pain relief, especially in the case of a nodular
type of MM.[66] Hermann et al.,[67] reported improvement in pain
in six out of 16 patients treated with craniospinal irradiation.
Management of hydrocephalus in malignant meningitis
MM can present with both communicating and
non‑communicating hydrocephalus. Hydrocephalus is a
common finding in MM.[68] Options available to tackle this
situation include 1. Ventriculoperitoneal shunt (VPS); 2.
Multiple lumbar punctures (LP); 3. Intraventricular reservoir
placement; 4. Endoscopic third ventriculostomy.[4,54] There is
no level I evidence for a preferred management option. Results
of various prospective and retrospective observation studies
on the role of intervention in MM‑associated hydrocephalus
and on the various management options suggest that the
decision‑making is multifactorial.
VPS is the most common procedure performed for MM‑associated
hydrocephalus [Figure 2]. All the studies reported significant
improvement in the hydrocephalus‑induced symptoms,
with improvement in the quality of life. Most of the patients
reported improvement in headaches and vomiting. However,
improvement in cognitive impairment, gait ataxia, and urinary
incontinence was less common. Shunt revision due to frequent
blockage was the most common complication reported. None of
the studies reported peritoneal dissemination of the disease.[69‑74]
Repeated LP offers a rapid symptom improvement but with
significant discomfort for the patient.[68,75] Lumboperitoneal
shunts have been reported as being effective as palliative
measures in MM‑related hydrocephalus. This shunt tends to
be less invasive and is easier to revise in case of an obstruction
than a VP shunt. Thus, it may be an favorable procedure in frail
MM patients.[76] The intraventricular reservoir placement offers
the painless repeated tapping of CSF along with a route for
administering intraventricular chemotherapy. The role of ETV
in MM‑associated hydrocephalus is expected to be restricted
to a subset of patients with obstructive hydrocephalus due to
bulky leptomeningeal disease. Gonda et al.,[77] compared the
outcome of ETV (in a selected group of patients with favorable
factors for ETV) with VPS (done in patients not meeting the
criteria for ETV). They concluded that even in the selected
population, the clinical outcomes and complication rates
were similar between ETV and VPS. Karnofsky’s performance
status (KPS), the type of primary pathology, and the dominant
 Kumar, et al.: Malignant meningitis with hydrocephalus

Table  1: Summary of the randomized controlled trials and clinical trials published in the last five years on malignant
meningitis secondary to carcinoma (CA) breast, CA lung and other solid tumors (PubMed search ‑((((leptomeningeal
carcinomatosis) OR (leptomeningeal metastasis)) OR (carcinomatous leptomeningitis)) OR (malignant meningitis)) OR
(meningeal carcinomatosis), Filters: Clinical Trial, Randomized Controlled Trial, in the last 5 years)
Trials Sample Tumor type Intervention/ End points Results Final remarks
size (n) Treatment arms
Non‑Small Cell Lung
Cancer (NSCLC)
Kim et al.[53] 2016 67 NSCLC Ceritinib in patients Overall response, ALK inhibitor‑naïve ALK inhibitor‑naive and
with ALK‑rearranged Duration of response: 13/20 (65%) ALK inhibitor‑pretreated
non‑small‑cell lung response, ALK inhibitor‑pretreated patient given ceritinib
cancer (ASCEND‑1): Progression‑free response: 5/18 (28%) 750 mg/day had durable
ALK inhibitor‑naïve survival and Safety responses and prolonged
and ALK progression‑free survival,
inhibitor‑pretreated along with a manageable
safety profile and low
frequency of study
discontinuation
Tamiya et al.[54] 11 NSCLC Afatinib (40 mg/day), Primary endpoint: CSF penetration rate: Afatinib was effective
2017 CSF penetration rate 2.45±2.91% against leptomeningeal
Secondary ORR: 27.3% (three out of carcinomatosis,
endpoints: 11 patients), and two out particularly in patients
with NSCLC harboring
Objective response of these three responders
had uncommon EGFR uncommon EGFR
rate (ORR),
mutations. mutations
progression‑free
survival (PFS), and The median PFS and OS
overall survival (OS) were 2.0 and 3.8 months,
respectively.
Yang et al.[55] 2019 41 NSCLC Osimertinib [a Objective response ORR: 41% (95% CI: Osimertinib showed
[LMs from third‑generation rate 26%‑58%), meaningful therapeutic
EGFR‑mutated epidermal growth (ORR), Duration of Median DoR: 8.3 months efficacy in the CNS and
NSCLC factor receptor response (DoR), (95% CI: 5.6‑16.5 months).a manageable safety
progressed (EGFR) tyrosine Progression‑free Median PFS: 8.6 months profile at 160 mg once
despite kinase inhibitor (TKI)] survival (PFS), (95% CI: 5.4‑13.7 months) daily in patients with
previous Overall survival (OS),with 78% maturity; EGFRm NSCLC with
EGFR‑TKI Pharmacokinetics LM.
Median OS: 11.0 months
therapy] (PK) and Safety. (95% CI: 8.0‑18.0 months)
with 68% maturity.
CSF tumor cell clearance
was confirmed in 11 (28%;
95% CI: 15%‑44%) of 40
patients.
Neurologic function
improved in 12 (57%) of 21
patients with an abnormal
assessment at baseline
Nosaki et al.[56] 21 NSCLC Erlotinib (150 mg per Objective cytological 1) Clearance rate was Erlotinib was active
2020 oral) clearance rate, 30.0% (95% confidence for LM and may be
Time to LM interval [CI]: 11.9%‑54.3%), a treatment option
progression (TTP), the median TTP was 2.2 for patients with
Overall survival (OS),months, and the median OS EGFR‑mutated NSCLC
was 3.4 months. and LM.
Quality of life
outcomes, and 2) Significantly longer
pharmacokinetics TTP and OS times were
observed in patients with
mutant EGFR (P=0.0054
and P<0.0001, respectively).
3) The mean cerebrospinal
fluid penetration rate was
3.31% ± 0.77%.
4) There was a good
correlation between plasma
and cerebrospinal fluid
concentrations
Contd...
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 Kumar, et al.: Malignant meningitis with hydrocephalus

Table 1: Contd...
Trials Sample Tumor type Intervention/ End points Results Final remarks
size (n) Treatment arms
Park et al.[57] 2020 80 EGFR Brain metastases BM cohort ‑ BM cohort ‑ intracranial 160 mg Osimertinib is a
(40+40) T790M‑positive (BM) intracranial objective ORR was 55%. In the safe and effective option
NSCLC Leptomeningeal response rate (ORR) BM cohort, the median for patients with BM or
progressed on metastases (LM) LM cohort ‑ OS PFS was 7.6 months, LM after prior EGFR TKI
prior EGFR TKI Osimertinib (160 mg, the median OS was 16.9 treatment
therapy per oral) months. In the LM cohort,
the median PFS was 8.0
months, the median OS
was 13.3 months
Breast cancer
Bonneau et al.[58] 16 HER2‑positive Dose‑escalation To determine the Eleven patients had no MTD and recommended
2018 breast cancer study of intrathecal maximum tolerated toxicity. phase II weekly dose
(IT) administration of dose For 60 mg or higher of IT trastuzumab in
trastuzumab dose levels, minor patients with HER2‑BC
toxicities attributed to IT and MC is 150 mg
trastuzumab included
headache (n=2), nausea
(n=2), vomiting (n=1),
cervical pain (n=1), and
peripheral neuropathy
(n=1)
Morikawa et al.[59] 11 Ca Breast 1) Phase I trial using Responses were 1) Grade 3 nausea 1) High‑dose lapatinib
2019 (HER2‑ an accelerated dose assessed by CSF and vomiting were is tolerable when
positive) escalation design cytology, radiology dose‑limiting toxicities. given intermittently
done imaging, and clinical 2) Maximum tolerated and sequentially with
2) Lapatinib was signs/symptoms dose of lapatinib was 1500capecitabine.
given on Day 1‑3 mg BD. 2) Antitumor activity
and Day 15‑17 with 3) Three patients was noted in both CNS
capecitabine on Day remained on therapy for and non‑CNS sites of
8‑14 and Day 22‑28 greater than six months disease.
on an every 28‑day 3) This novel
cycle. administration regimen is
3) Lapatinib dose feasible and efficacious
was escalated, and in HER2‑ positive breast
capecitabine given cancer patients with CNS
as a flat dose at metastasis and warrants
1500 mg BD further investigation.
Le Rhun et al.[60] 73 Ca Breast Systemic therapy Progression‑free Median LM‑PFS was 2.2 Addition of intrathecal
2019 (37+36) alone (control group) survival related to months in the control liposomal cytarabine
or systemic therapy LM (LM‑PFS) versus 3.8 months in the to systemic treatment
plus intrathecal experimental group. improves LM‑related
liposomal cytarabine Median OS was 4.0 PFS.
(experimental group) months in the control
versus 7.3 months in the
experimental group.
Mrugala et al.[61] 3 Ca Breast Intravenous high Progression‑free Median PFS was 1.4 Combination of systemic
2019 dose methotrexate survival (PFS) months (range: 1.3‑8.2 therapy with intrathecal
at 8 g/m2 with months) and approach appears to be
intrathecal liposomal Median overall survival very feasible, especially
cyatarabine (OS) was 8.2 months in patients who have an
(range: 5.5‑11.3 months) intraventricular catheter

Contd...

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 Kumar, et al.: Malignant meningitis with hydrocephalus

Table 1: Contd...
Trials Sample Tumor type Intervention/ End points Results Final remarks
size (n) Treatment arms
Pan et al.[62] 2016 59 Solid tumors Concurrent Primary endpoint: Overall response rate was IC combined with
therapy consisted ‑ Clinical response 86.4% (51/59). OS ranged concomitant IF‑RT, with
of concomitant rate. from 0.4 to 36.7 months significant efficacy and
IC (methotrexate Secondary endpoint: (median 6.5 months), and acceptable toxicity may
12.5‑15 mg and 1‑year‑survival rate was be an optimal therapeutic
‑ Overall survival
dexamethasone 5 21.3%. option for treatment of
(OS)
mg, weekly) and LM from solid tumors
IF‑RT (whole brain ‑ Safety with adverse prognostic
and/or spinal canal factors.
RT, 40 Gy/20f).
For patients with
low (KPS) scores
and radiotherapy
intolerance, induction
IC (1‑3 times)
was given before
concurrent therapy
Utz et al.[63] 2018 47 Primary Comparison of 2D‑FLAIR, SPGR, 10 cases with more 3D‑FLAIR identified
brain tumors the sensitivity of and 3D‑FLAIR leptomeningeal signal more LSAs compared
(Pediatric) 3D‑FLAIR and SPGRimages were abnormalities on with SPGR.
in the evaluation analyzed and 3D‑FLAIR. Future analyses should
of leptomeningeal recorded the Overall, there were determine whether the
signal abnormalities total number of significantly more lesions time dependence of
(LSA) parenchymal lesions on 3D‑FLAIR than spoiled gadolinium enhancement
and LSAs in each gradient echo sequences affects the sensitivity
study, up to 30. If of 3D‑FLAIR, and
>30 lesions were should include patients
seen they were with pathology‑proven
considered too leptomeningeal disease.
numerous to count.
Malani et al.[46] 15 Breast, colon Sequential CSF CSF from patients Radiographic LM was Enumeration of CSF
2020 CTC enumeration was obtained on documented in 14 (93%) CTCs is a more accurate
in patients with LM day 1 of each cycle patients. measurement of tumor
from HER2+cancers and was evaluated CSF cytology was positive burden in the CNS than
receiving intrathecal by the CellSearch® in 6 (40%) and CSF CTCs standard CSF cytology
(IT) trastuzumab to platform for CTC were identified in 13 (87%)and can be used as a
capture dynamic enumeration. patients. biomarker of treatment
changes in CSF CTC The results were Median CSF CTC was 22 response.
enumeration correlated with CTCs (range: 0‑200+) per
CSF cytology from 3 ml.
the same sample,
HER2/neu expression
along with clinical
analysis of CTCs was
and radiographic
performed in 8 patients;
response.
75% had confirmed
expression of HER2/
neu positivity in CSF and
HER2/neu expression was
absent in 25%.
Four of 10 patients
received 7 or more cycles
of IT trastuzumab; in 3 of
these patients, increase in
CSF CTCs enumeration
from baseline was
detected 2‑3 months prior
to changes seen on MRI,
and while CSF cytology
remained negative.

Contd...
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 Kumar, et al.: Malignant meningitis with hydrocephalus

Table 1: Contd...
Trials Sample Tumor type Intervention/ End points Results Final remarks
size (n) Treatment arms
Yang et al.[64] 2020 24 Solid tumors Proton craniospinal Primary endpoint: Median CNS PFS was Hypofractionated proton
irradiation (CSI) treatment‑related 7 months (95% CI 5‑13) CSI using proton therapy
toxicity, with and the median OS was 8 is a safe treatment for
dose‑limiting toxicity months (95% CI 6) patients with LM from
Secondary Four patients (19%) were solid tumors.
endpoints: CNS progression‑free in the Durable disease control
progression‑free CNS for more than 12 is seen in some patients.
survival (PFS) and months.
Overall survival (OS).Two patients in the
dose‑expansion cohort
experienced DLTs
consisted of Grade 4
lymphopenia, Grade 4
thrombocytopenia, and/or
Grade 3 fatigue.
All DLTs resolved without
medical intervention
Brastianos et al.[65] 20 Solid tumors Pembrolizumab Primary endpoint: The median follow‑up of Pembrolizumab is safe
2020 (200 mg Rate of overall surviving patients was 6.3 and feasible and displays
intravenously survival at 3 months months (range, 2.2‑12.5 promising activity in
every 3 weeks until (OS3). months). patients with LMD.
definitive progression Secondary The percentage of Further investigations
or unacceptable objectives: patients who experienced are needed to identify
toxicity) Toxicity, one (or more) grade 3 or which patients with
higher adverse events, LMD can benefit from
Response rate and
at least possibly related Pembrolizumab.
Time to intracranial to treatment, was 40%,
or extracranial the most frequent being
disease progression hyperglycemia (n=6),
nausea (n=7), and
vomiting (n=7).
The study met the
primary endpoint, as 12
of 20 (OS3, 0.60; 90%
confidence interval,
0.39‑0.78) patients were
alive at 3 months after
enrollment
[Intrathecal chemotherapy (IC); Karnofsky performance status score (KPS); Involved‑field radiotherapy (IF‑RT); Leptomeningeal signal abnormalities (LSAs);
Spoiled gradient echo (SPGR) sequence; Leptomeningeal metastasis (LM); Circulating tumor cells (CTCs)]; Leptomeningeal disease (LMD)

presenting symptoms have been identified as significant factors Radiotherapy

in the decision‑making for surgical intervention. Though
benefit has been reported in patients with both a good and a bad
KPS, it was better in a patient with KPS ≥ 30.[69] Intervention
for hydrocephalus improves the general condition, allowing for
the administration of more aggressive therapy for the primary
pathology. It accounts for improvement in the overall survival
in patients with diseases that are amenable to existing therapies,
such as breast cancer, lymphoma, and leukemia.[74,78] Mitsuya
et al.,[79] in a retrospective study, found this intervention to be
safe and effective in adenocarcinoma of the lung.
A significant number of patients may not be surgical candidates
due to the presence of an advanced primary disease and a
poor general condition. Thus, the type of intervention should
be tailored for each patient based on the favorable factors,
including a good general condition, controlled primary disease,
headache or nausea as dominant symptoms, and availability of
effective treatment options for the primary pathology.
The role of radiotherapy in the management of MM has been
as a part of multimodal treatment, along with chemotherapy.
It has been mainly utilised as a palliative therapy. The various
modes of radiotherapy used for MM include whole‑brain
radiotherapy (WBRT), craniospinal irradiation (CSI), and
focal brain radiotherapy (FBRT). FBRT (20–40 Gy in daily
fractions of 2–4 Gy) involves administering radiation to
a limited zone and avoids the complications of WBRT/
CSI (leukoencephalopathy/myelosuppression). It includes
fractionated or stereotactic radiosurgery (SRS), focal spine
radiotherapy (FSRT), intrathecal chemoradiotherapy (ITCRT),
and intraventricular radioisotope administration.
There is no level I evidence that has assessed the role of
radiotherapy alone. Most studies included RT as an adjunctive
therapy. Few case series have reported outcomes of palliative
radiotherapy in terms of improvement in symptoms and overall
survival. Shafie et al.,[80] reported effective symptom stabilization

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 Kumar, et al.: Malignant meningitis with hydrocephalus

a b c
Figure 2: A patient with (a) axial T2 weighted MRI showing a posterior third ventricular round cell tumor who underwent a ventriculoperitoneal shunt for hydrocephalus (b). (c)
Sagittal T2 weighted MRI showing multiple contrast‑enhancing drop metastases.The patient had manifestations of malignant meningitis. Despite a patent aqueduct of Sylvius
and an open fourth ventricular outlet, the subarachnoid adhesions resulted in the development of symptomatic hydrocephalus (curved arrow).

and even syptomatic improvement in up to 75.5% of their
patients (N = 110). In a pathologically heterogeneous cohort treated
with radiotherapy and chemotherapy, they reported a median
overall survival of 13.86 weeks (IQR: 7.14–32.00) after establishing
the presence of MM. Most studies confirmed a significant
improvement in symptoms, while the benefit in overall survival
was inconsistent in MM due to solid tumors.[66,67,81‑83] Contrary to
this, RT was found to induce a long‑term, disease‑free survival in
MM secondary to chronic lymphocytic leukemia and diffuse large
B‑cell lymphoma.[84‑88] Other pathologies where RT has shown to be
effective in bringing about a significant symptomatic improvement
as monotherapy include esthesioneuroblastoma, pediatric CNS
glioma, pediatric rhabdomyosarcoma, and gynecological
cancers (ovarian cancer, cervical cancer, and endometrial cancer).
Hypofractionated proton craniospinal irradiation (CSI) was
reported to be safe and effective in disease control in MM from
solid tumors in a recent phase I prospective trial.[64]
Chemotherapy – systemic and intrathecal chemotherapy
Chemotherapy for MM can be administered systemically or
intrathecally. The blood–brain and blood–CSF barriers disallow
therapeutic levels of chemotherapeutic agents to be achieved
in the CSF, on systemic administration. Though this barrier
is breached in MM, the degree of penetration of the chemo
therapeutic agent is variable and inadequate. Direct intrathecal
instillation of the drugs overcomes this limitation. In addition,
intrathecal chemotherapy allows for the tumor exposure to a
higher drug concentration with minimum systemic toxicity,
lower dose requirement, and longer duration of exposure to the
drug (due to a longer t1/2). However, the intervention is limited
by procedure‑related complications due to the performance
of repeated lumbar punctures or due to the intraventricular
instillation of the drug. The presence of CSF flow alteration
due to MM, and an uneven distribution of the drug can lead to
an ineffective treatment, significant neurotoxicity, and raised
intracranial pressure (ICP).[89] The penetration of the drug into
the bulky disease is also limited when it is given through the
intrathecal route (the approximate penetration is 2–3 mm only).[2]
In these situations, systemic therapy is helpful. It allows for control
of the primary disease along with the MM. Multiple trials have
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S451
evaluated the role of different drugs, for both routes. No RCTs
exist that are comparing the efficacy of one route over the other.
The common drugs used for systemic chemotherapy include
capecitabine, cisplatin, carboplatin, gemcitabine, vinorelbine,
4‑fluro‑uracil, pemetrexed, methotrexate (3–8 gm/m 2),
thiotepa, temozolomide, and etoposide.[90‑100]
Methotrexate, thiotepa, cytarabine, and liposomal cytarabine
are the common drugs used for intrathecal chemotherapy.[52]
Depending on the location of the lesion, the drugs can be
instilled intraventricularly or intrathecally in the lumbar region.
An intraventricular catheter (Omaya reservoir) allows for
repeated instillations of the intraventricular without pain.
A  CSF flow study is a prerequisite to ascertain the absence
of CSF flow obstruction. Ommaya reservoir intraventricular
installation of drugs is suitable for the treatment of diffuse
leptomeningeal involvement.
In a randomized controlled trial (DEPOSEIN trial) on patients
of metastatic breast cancer, Rhun et al.,[60] compared systemic
chemotherapy alone (control group) and systemic therapy
plus intrathecal liposomal cytarabine (experimental group).
They concluded that adding intrathecal liposomal cytarabine to
systemic treatment improved the MM associated progression‑free
survival (PFS) (was 2.2 months in the control vs. 3.8 months in the
experimental group) and median overall survival (OS) (4.0 months
in the control vs. 7.3 months in the experimental group). Mrugala
et al.,[61] also reported that in patients with carcinoma breast with
MM, a combination of systemic therapy with intravenous high
dose methotrexate at 8 g/m2 and intrathecal liposomal cytarabine
is feasible resulting in a PFS of 1.4 months (range: 1.3–8.2) and
median OS of 8.2 months (range: 5.5–11.3). Though intrathecal
liposomal cytarabine has been shown to have improved survival
outcomes as compared to other chemotherapeutic agents, it caused
significant chemical arachnoiditis, requiring co‑administration of
dexamethasone and intravenous hydration.[86,87]
Ventriculo‑lumbar perfusion (VLP) is advantageous over the
conventional intraventricular therapy in preventing raised
 Kumar, et al.: Malignant meningitis with hydrocephalus
intracranial pressure. Choi et al.,[102] reported that a reduced
rate of VLP, at 15 mL/h, with methotrexate reduced the side
effects and prolonged the OS in a study population consisting
of mostly non‑small cell lung cancer (NSCL), as an interim
result of their Phase II study.[103,104]
Targeted therapy
As liposomal cytarabine is no longer commercially available,
and other drugs for intrathecal therapy have a limited
benefit and an inconvenient dosing, the search has extended
to intrathecal targeted therapeutic agents. Intrathecal
trastuzumab (150 mg intrathecal weekly) was found to
be effective and safe in controlling MM in HER‑2 positive
carcinoma breast.[58,105,106] The role of intrathecal nivolumab
in MM associated with melanoma and lung cancer is being
evaluated in an ongoing trial (NCT03025256).[107]
Recent trials have reported a positive response with ceritinib,
afatinib, osimertinib, and erlotinib in cases of non‑small cell lung
cancer (NSCLC) with MM. Morikawa et al., reported the combined
administration of lapatinib and capecitabine as an effective
regimen for HER2+ breast cancer patients with CNS metastasis.[59]
Prognosis
A combination of focal radiotherapy and chemotherapy
(intrathecal or systemic) constitutes the standard treatment of
MM. The type of primary cancer is a major prognostic factor.
Wasserstrom et al.,[7] published the result of 90 MM patients
after focal irradiation and intraventricular methotrexate; 61%
of breast cancer patients showed a neurological improvement
within 2–20 months. Median survival in this group was
7.2 months and 15% of patients were alive at 1 year. In contrast,
only 39% and 18% patients of the lung carcinoma and melanoma
group, respectively, improved or remained stable within a range
of 1–12 months, with a median survival of 3–4 months and a
0% survival rate at 1 year. Median survival of MM from breast
cancer can reach at least 6 months, which is superior to the
observed survival in untreated patients, which is approximately
10 weeks, as reported by many authors.[87,88,96‑100] Apart from the
primary disease, other factors that confer a worse prognosis
include a poor Karnofsky Performance Status (KPS) (<60), as
well as the presence of encephalopathy, bulky CSF disease, and
extensive systemic cancer.[108-112]
Conclusion
Significant attempts have been made recently to standardize
the diagnosis and assessment of treatment outcome; however,
a definitive protocol is still under evolution. Intrathecal
chemotherapy is a safe and effective adjunct to systemic
chemotherapy and radiotherapy. The role of targeted therapy
is expanding. Despite these advances, the overall survival
in these patients has seen only a little improvement. The
present management goal, including of treating the associated
hydrocephalus, in the case of MM is still palliative, with
attempts being made to improve the quality of life.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
S452 Neurology India | Volume 69 | Supplement 2 | November-December 2021
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 Review Article

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Quick Response Code:
Spontaneous Intracranial
Hypotension ‑ A Dilemma
Dhaval Shukla, Nishanth Sadashiva, Jitender Saini1, Sriganesh Kamath2

Website: Abstract
www.neurologyindia.com
Background: Spontaneous intracranial hypotension (SIH) is a highly misdiagnosed and underdiagnosed
DOI: disorder.
10.4103/0028-3886.332255 Objective: Update evaluation and treatment of spontaneous intracranial hypotension.
Methods and Material: Narrative review.
Results: Traditionally, SIH is diagnosed when a headache has developed spontaneously and in temporal
relation to a CSF leak (evident on imaging) and/or CSF hypotension (lumbar puncture opening pressure <60 mm
CSF). However, lumbar puncture is not mandatorily required to diagnose SIH. Besides headache, other
symptoms such as nausea/vomiting in 50.6%, neck pain/stiffness in 33%, tinnitus in 19%, dizziness in 14%,
hearing disturbances in 10.7%, followed by visual disturbances, vertigo, back pain, and cognitive symptoms
may be present. In suspected cases of SIH, brain and spine should be evaluated with MRI. Dynamic
computerized tomographic myelography is required to demonstrate the site of spinal CSF leak. Epidural blood
patch (EBP) is a minimally invasive treatment for spontaneous intracranial hypotension (SIH) refractory to
medical management and provides symptomatic relief in up to 90% of patients even in patients with bilateral
subdural hematomas. The CSF‑venous fistulas do not respond well to EBP, and the most definitive curative
treatment is the surgical closure of the fistula.
Conclusions: The SIH is a distinct entity and requires a high index of suspicion for diagnosis. A post‑contrast
MRI should be included for evaluation of headaches. Spinal MRI should be done to demonstrate the site of
leak. Epidural blood patch therapy is the most effective treatment of SIH. Most SDHs associated with SIH
do not require treatment.
Key Words:
Brain sagging, CSF leak, headache, intracranial hypotension, myelogram

Key Message:
Spontaneous intracranial hypotension results in postural headache, and the diagnosis is often missed.
Intracranial hypotension should be suspected in patients with spontaneous bilateral subdural hematomas.
Epidural blood patch is the most effective treatment of spontaneous intracranial hypotension.

Departments of

1
Neurosurgery,
Neuroradiology
S pontaneous intracranial hypotension (SIH) is a
misdiagnosed and underdiagnosed disorder.
It is not uncommon, with an annual incidence
pressure <60 mm CSF).[4] However, currently,
there is uncertainty on reliable diagnosis and
treatment of SIH.
and Interventional
of 5 per 1,00,000 individuals every year.[1] The
Radiology and
SIH syndrome was originally described by the Clinical features
2
Neuroanesthesiology
German neurologist Schaltenbrand in 1938 as SIH can occur at any age. It can occur in both
and Neuro Critical
hypoliquorrhea.[2] SIH is defined as a clinical sexes with a predilection for females (63%).[3]
Care, National Institute
condition characterized by debilitating postural The mean duration of symptoms at the time of
of Mental Health
headaches secondary to spontaneous spinal diagnosis is one month. There is a great diversity
and Neurosciences,
cerebrospinal fluid (CSF) leak and/or CSF of signs and symptoms. Orthostatic headache,
Bengaluru, Karnataka,
hypotension.[3] In the International Classification once believed to be an essential characteristic
India
of Headache Disorders (ICHD), 3 rd edition, of SIH in earlier ICDH criteria, is not invariably
Address for SIH is diagnosed when a headache develops present. In a review of clinical features, 8% of
correspondence: spontaneously and in temporal relation to patients had a nonorthostatic headache and
Dr. Dhaval Shukla, a CSF leak (evident on imaging) and/or 3% did not experience headaches.[3] Headache
Professor of Neurosurgery, CSF hypotension (lumbar puncture opening
National Institute of Mental
Health and Neurosciences This is an open access journal, and articles are distributed under the terms How to cite this article: Shukla D, Sadashiva N, Saini J,
(NIMHANS), of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 Kamath S. Spontaneous Intracranial Hypotension - A
Bengaluru ‑ 560 029, License, which allows others to remix, tweak, and build upon the work Dilemma. Neurol India 2021;69:S456-62.
Karnataka, India. non‑commercially, as long as appropriate credit is given and the new
creations are licensed under the identical terms. Submitted: 12‑Jun‑2021   Accepted: 08‑Sep‑2021  
E‑mail: neurodhaval@ Published: 11-Dec-2021
rediffmail.com For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com

S456 © 2021 Neurology India, Neurological Society of India | Published by Wolters Kluwer - Medknow
 Shukla, et al.: Intracranial hypotension

generally occurs or worsens within 15 minutes of assuming the

upright position and improves within 15–30 minutes after lying
down.[5] Headache is frequently occipital, frontal, or diffuse.
Other presenting symptoms in descending order reported are
nausea/vomiting in 50.6%, neck pain/stiffness in 33%, tinnitus
in 19%, dizziness in 14%, hearing disturbances in 10.7%, followed
by visual disturbances, vertigo, back pain, and cognitive
symptoms.[3] Other rare presentations reported include multiple
cranial nerve palsies,[6] cortical/cerebral vein thrombosis,[7]
quadriplegia and cerebellar hemorrhage, [1] movement
disorders,[8] brain sagging syndrome,[9] status epilepticus,[10]
spine disease,[11] and coma.[12] The clinical mimickers of SIH a b
are postural orthostatic tachycardia syndrome, orthostatic
Figure 1: (a) Axial FLAIR image shows pachymeningeal thickening, which appears
hypotension, cervicogenic headache, and vestibular migraine.[13]
hyperintense. (b) Axial T2W image shows focal thickening in the left frontal location;
however, it appears inconspicuous
Pathology and pathophysiology
SIH usually occurs due to spontaneous CSF leaks typically
located at the nerve root sleeves at the level of the cervical or
thoracic spine. It is thought to occur following trivial trauma
such as sports activities, trivial falls, coughing, or sneezing,
though the exact cause is not known. Epidural hypotension is
also believed to be caused due to a negative pressure within
the inferior cava transmitted to the epidural space, resulting
in aspiration of CSF.[14,15] The correlation between SIH and
connective tissue disorders supports the hypothesis of a dural
compliance disorder as the main cause for this syndrome[1,16,17]
Many patients with SIH have normal (and occasionally high)
lumbar puncture opening pressure. CSF pressure is normal a b
in 32% of patients and may be related to inadequate methods
of measurement or the actual absence of a low CSF pressure Figure 2: (a) Coronal T1W post-contrast image shows pachymeningeal thickening
and enhancement. Bilateral transverse sinuses appear engorged and prominent.
state. Lumbar puncture opening pressure is a snapshot method
(b) T2W images show similar findings with bilateral subdural collection
of measurement. It is not reflective of the ICP in the upright
position and does not offer any information regarding the CSF
dynamics during a postural change. Lumbar punctures have
good sensitivity (67%) and can support the diagnosis of SIH;
however, a normal opening pressure does not exclude this
disorder.[3] Up to 32% of patients may have normal and 3%
may have mildly raised opening pressures.[3,18,19]

There are no pathological findings in SIH. In one of the

cases, meningeal biopsy was performed, which showed
only fibroblasts and small thin‑walled blood vessels in an
amorphous matrix.[20]

Sequelae of intracranial hypotension

To keep the intracranial pressure (ICP) constant, the volume
loss of one compartment is compensated by an increase in the
volume of the other compartments (Monro–Kellie doctrine).
When the CSF is lost gradually, compensation mainly occurs
through an increase of the cerebral blood volume, especially
Figure 3: Sagittal T2W image shows engorged transverse sinus.
of the venous blood. If CSF is lost rapidly, the brain tissue
is displaced and damaged. Persistent negative pressure
in the subarachnoid space leads to tearing of bridging suspected cases of SIH, brain and spine should be evaluated.
veins or bleeding from engorged veins leading to subdural Spine imaging is useful for planning the therapy.
hematoma (SDH). Chronic SDHs are known to occur in
16%–57% of patients. When nontraumatic and bilateral SDH Brain MRI
at middle age is encountered, association with SIH should be The characteristic MRI finding is diffuse pachymeningeal
considered as one of the causes.[21] thickening and enhancement.[22] Imaging can mimic meningitis
on MR imaging.[23] Diffuse pachymeningeal enhancement may
Imaging also be absent in some cases of SIH as it has been reported
Magnetic resonance imaging (MRI) in patients with SIH is usually to disappear in long‑standing cases.[24] Other MRI findings
performed as a part of headache evaluation [Figures 1–7]. In are inferior sagging of the brain across the tentorial hiatus
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S457
 Shukla, et al.: Intracranial hypotension
a b
Figure 4: (a) Coronal T1W post-contrast image shows enlarged pituitary gland with
convex superior surface. (b) Sagittal T1W post-contrast image shows enlarged
pituitary gland with effaced suprasellar cistern space.
a b
Figure 6: (a) Spine T2W images showing epidural collection and engorged epidural
veins. (b) Findings are much better appreciated on axial T2W images.
and foramen magnum, pituitary enlargement, subdural
fluid collections, posterior lobe pituitary hematomas, venous
distention in the intracranial compartment, diffuse spinal
dural enhancement, spinal epidural fluid collection and
engorgement of the epidural venous plexus, and abnormal
intensity around the root sleeves.[22,25–27] On fluid‑attenuated
inversion recovery (FLAIR) images, thickened meninges
appear hyperintense and can be used to distinguish it from
the CSF, which appears hypointense; similarly, subdural
collections can be easily identified.[28] Inferior displacement of
the brain or “sagging of the brain” is characterized by effaced
perichiasmatic and prepontine cisterns, inferior displacement
of cerebellar tonsils or optic chiasm, descent of the cerebral
aqueduct, decreased pontomamillary distance, and effacement
of subarachnoid spaces on brain MRI.[22,25,28] Inferior descent
of the brain may lead to the stretching of the bridging veins
in subdural spaces, which may rupture and cause subdural
hematomas. [26] CSF extravasation through permeable
microvessels of the dura mater may lead to the formation of
bilateral frontoparietal subdural effusions.
Pituitary gland enlargement is a subjective observation and can
be difficult to identify because of gender and age differences.
Alvarez‑Linera et al.[29] considered the gland enlarged when
the mean height of the gland was 1.5 times greater than the
normal height, which is between 4.2 and 4.8 mm in healthy
S458 Neurology India | Volume 69 | Supplement 2 | November-December 2021
a b
Figure 5: (a) Axial FLAIR image shows subdural effusion bilaterally appearing
hyperintense. (b) Similar findings noted on coronal T2W images.
Figure 7: Sagittal T2W images showing decreased mamillopontine distance and
decreased prepontine distance.
post‑pubertal females and 3.5  mm in healthy adult males.
Pituitary hemorrhage is another feature described in association
with SIH and is likely to be of venous origin. Another sign
described in relation to the pituitary gland is the enlarged
inter cavernous sinus best seen on sagittal T1W images.[30]
Meta‑analysis of 2078 scans showed diffuse pachymeningeal
enhancement in 73%, subdural collections in 35%, brain sagging
in 43%, venous engorgement in 57%, and pituitary gland
enlargement in 38%. Brain MRI was normal in 19% of patients.[3]
Dobrocky et al.[31] described a novel scale based on MRI findings
to help in deciding about the need for invasive techniques
to identify the possible CSF leak in patients presenting
with orthostatic headache. They analyzed nine quantitative
parameters and seven qualitative parameters. Based on
logistic regression analysis they identified pachymeningeal
enhancement, engorgement of venous sinus, and effacement
of the suprasellar cistern of 4.0 mm or less as major findings
and were assigned a score of 2 while three were considered
minor (1 point each), which included subdural fluid collection,
effacement of the prepontine cistern of 5.0 mm or less, and
mamillopontine distance of 6.5  mm or less. Patients were
classified into three groups, namely low, intermediate, or
high probability of having a spinal CSF leak, with scores of 2
points or less, 3–4 points, and 5 points or more, respectively,
on a scale of 9 points.
 Shukla, et al.: Intracranial hypotension

Spine MRI Treatment

Spinal MRI abnormalities are detected in most patients
with SIH in the form of epidural vein distension in the
anterolateral epidural space of the upper cervical or
thoracolumbar regions and fluid collection along the nerve
root sleeves in the thoracic region.[27] SIH is commonly caused
by leakage of CSF through the spinal dural sac and can be
divided into three patterns: fast leaks, slow leaks, and cases
in which no leak is visible. Techniques used for detection of
CSF leaks include myelography, computerized tomographic
myelography (CTM), radioisotope cisternography, and
magnetic resonance myelography (MRM). CTM can
indicate the level and the site of leaks but it is invasive,
time‑consuming, and delivers significant radiation to the
patients. Radioisotope cisternography or conventional
spinal MRI can be used as guides to determine adequate
CT myelography scanning levels. In cases of high flow leak,
CTM may not be able to precisely locate the site of the leak;
in such cases, dynamic CTM can be used. Digital subtraction
myelography is another useful technique for detecting
high‑flow leaks but issues are planar images and need for
excellent patient cooperation during examination. MR using
T2 fat sat imaging is another useful technique where epidural
fluid collection may be seen, and a large epidural pooling
is suggestive of a high‑flow leak. Slow‑flow leak may be
identified as focal CSF fluid seen around a nerve root or in
the vicinity of an osteophyte. Retrospinal collection at the
C2–C3 level is a false localizing sign and does not necessarily
indicate leakage site.[27] In cisternography indium labeled
diethylenetriaminepentaacetic acid  (DTPA) is also used
for identifying the site of leak. A radiopharmaceutical is
injected intrathecally followed by imaging at 1, 2, 4, and 24 h.
Leak is seen as focal excess radioactivity in the paraspinal
tissue. Indirect signs are early activity in the kidney and
bladder (<4 h), rapid loss of spinal activity, and absence of
cerebral convexity at 24 h.[32] The yield of spine MRI for the
site of CSF leak ranges from 48% to 67%.[3] Contrast‑enhanced
MR cisternography serves as a useful diagnostic method in
cases where the site of dural defect is difficult to identify.
Intrathecal gadopentetatedimegulmine has been found to be
safe with no complications. Most of the studies have used
0.5 ml of intrathecal contrast diluted in 5 ml of CSF given
slowly over 3–5 min.[33]
Medical
Though the best type and duration of conservative management
is not clear, all patients should be tried with conservative
management as the first choice. Strict bed rest, plenty of
caffeine intake, avoiding sitting upright, and the addition of
analgesics are included in conservative management. High
intake of salt, oral, or intravenous hydration help in restoring
the volume of the CSF, which in turn alleviates the symptoms.[35]
A significant proportion of patients (28%) successfully respond
to conservative treatment measures.[3]
Epidural blood patch
Epidural blood patch (EBP) is a minimally invasive treatment for
SIH refractory to medical management and provides symptomatic
relief in up to 90% of patients.[36] Nonimprovement of symptoms
of SIH after a 1‑week trial of conservative management  (bed
rest, hydration, caffeine, and analgesics) is an indication for
performing EBP.[37] In patients with documented CSF leak sites
or those with significant neurological symptoms such as coma
or rapidly deteriorating consciousness attributable to SIH, early
EBP is desirable. Local infection, septicemia, bleeding disorders,
and patient refusal are contraindications for performing EBP.
The EBP may be performed blindly using knowledge about the
anatomical landmarks or with fluoroscopic guidance, which
can confirm the epidural space by contrast injection [Figure 8].
Using aseptic precautions, the Tuohy needle is secured in the
epidural space at the desired level using the loss of resistance
technique, and the patient’s own blood (autologous), obtained
mostly from the peripheral vein, is injected into the epidural
space. If the site of CSF leak is identifiable on an imaging study,
which is often in the cervical or cervicothoracic region, targeted
EBP is performed at or close to the site of the leak.[38] If the
site is not identifiable, an empirical lumbar EBP is performed.
The volume of EBP depends on the site of placement and is
approximately 4–6 ml at cervical, 10–12 ml at thoracic, and
20–30 ml at the lumbar region. Large EBPs (>20 mL) provide
higher success, but there is no difference between targeted
and nontargeted EBPs.[3] A single EBP is effective in 64%
of patients.[3] Nonresponders may require multiple EBPs.
The number of EBPs before determining a failure and time

Cerebrospinal fluid‑venous fistula

CSF‑venous fistula (CVF) is a type of CSF leak that is formed
due to an aberrant communication between the CSF space of
the root sleeve with the segmental spinal vein so that the CSF
flows into the venous channel due to higher CSF pressure
as compared to the venous channel. It clinically presents
with features of SIH.[24,34] Most of the lesions are located in
the thoracic region. MRI of the spine with high‑resolution
T2‑weighted images is usually the first investigation in
these cases and may show commonly described features of
intracranial hypotension. No studies have described any
specific features of CSF‑venous fistula. Patients with suspected
CVF should undergo dynamic subtraction myelogram (DSM)
or dynamic CT myelography (DCTM) in lateral decubitus
position to better delineate the leak. CT myelogram studies
may show hyperdense paraspinal vein with attenuation of Figure 8: Injection of contrast in epidural space in cervical spinal before blood
more than 70 HU. injection.

Neurology India | Volume 69 | Supplement 2 | November-December 2021 S459

 Shukla, et al.: Intracranial hypotension
gap between performances of subsequent EBP is not clear.
Generally, if the symptoms do not improve after three EBP
procedures, further EBP should not be considered and other
options such as surgery should be explored. A 48–72 ‑h time
gap between two EBPs may be preferred as symptomatic
improvement can occur till such time after the procedure.
While most patients respond well to EBP, predictors of
success are unclear. In a study comparing poor  (≥3 EBP
for symptomatic relief) and good responders  (≤2 EBP), the
clinical features, radiological findings, level of CSF leakage,
and volume of blood administered were not different between
the groups.[39]
The most common symptom of SIH is an orthostatic headache
that occurs from loss of CSF volume from spinal dura mater,
resulting in lower CSF pressure. The precise mechanism by
which EBP relieves headaches is unclear. One hypothesis
suggests the formation of a plug at the site of the dural
defect after EBP which blocks the CSF leak and restores CSF
pressure to relieve the headache. The second hypothesis is
that an increase in epidural pressure after placement of EBP
compresses the dura mater and increases the CSF pressure to
normal, thus ameliorating the SIH symptoms.[40]
The EBP is a simple and safe procedure in experienced hands
and results in prompt relief of symptoms. It can be performed
as a daycare procedure and is cost‑effective compared to the
more invasive surgery which requires hospitalization. EBP
can also be repeated to improve success. Disadvantages are
invasive (minimal) nature compared to conservative medical
management, need of imaging to confirm correct placement,
and risk of complications. The failure rates and number of
treatments needed are higher if the site of CSF leak is not
visualized or when EBPs are performed at the lumbar region.
Careful monitoring and assessment are needed during and
after EBP for early detection and management of complications.
Though rare, some of the potential complications include
neurological symptoms from spinal cord compression
with epidural blood, accidental subarachnoid puncture
and iatrogenic CSF loss causing aggravation of headache,
subarachnoid spread of epidural blood, and infection. The
complications are more likely when performed at the cervical
or thoracic level as compared to the lumbar level due to the
potential for cord damage.
Surgery
Surgery is reserved for patients in whom nonsurgical measures
have failed and for cases with bony abnormalities or meningeal
diverticula, in which sealing of the CSF leak by EBP is unlikely
to be effective.[5] If the defect is large, epidural patch therapy
may not be contemplated. The dural rent is identified and
closed using a muscle patch.[33] Beck et al.[41] reported that
almost all cases of longitudinal dural slit located ventrally
were associated with discogenic micro spurs piercing the dura
like a knife. Though anterior, posterior, and posterolateral
approaches have been described to reach the site of the dural
tear, a recent study of surgical approaches by Beck et al.[41]
proposed a posterior‑only approach to effectively reach any
site of CSF leak.[41] In this study reporting surgery for 47 cases,
they classified CSF leaks anatomically to type  I ventral, II
S460 Neurology India | Volume 69 | Supplement 2 | November-December 2021
lateral (including nerve root exit, lateral, and dorsal dural
sac), and III foraminal. Leaks anterior to the spinal cord were
approached by a transdural trajectory; 17 leaks lateral to the
spinal cord were approached by direct extradural trajectory and
two foraminal leaks by a foraminal microsurgical trajectory.
CVFs do not respond well to EBP, and the most definitive
curative treatment is the surgical closure of the fistula.[24,42]
Surgical ligation is effective for patients with CVF and SIH.[43]
In a study involving 24 patients, the mean headache severity
had significantly decreased after surgical intervention, with
everyone reporting high levels of satisfaction. Of note, 70%
of patients experienced symptoms of rebound intracranial
hypertension. All of them could be managed conservatively,
with a few patients requiring short‑term carbonic anhydrase
inhibitors. Recently, endovascular cannulation of the draining
vein and its embolization using onyx has also been described.[44]
Management of SDH
Some patients with SIH develop intracranial hematoma, which
also contributes to headaches. Literature is a bit confusing,
with some authors recommending evacuation of subdural
fluid in cases of deteriorating consciousness and few others
recommending EBP first even in patients with comatose
state.[45,46] Performing EBP first can increase intracranial pressure
and headache, while performing hematoma evacuation can
aggravate intracranial hypotension and headache.
Several complications, morbidities, and mortalities have been
reported with this association.[47–50] Some reports even mention
that surgery may cause deterioration due to acute brainstem
displacement provoked by opening the intrathecal space to
atmospheric pressure and that surgery increases the risk of
brain herniation.[45,50] In a large case series including 35 patients
with SDH due to SIH, 27 cases were treated by initial lumbar
EBP after conservative therapy; 17 (62%) patients recovered,
while 10 (37%) patients presented an enlarged SDH after the
EBP.[21]
Patients who develop chronic SDH may manifest only mild
neurological deficits and do not require treatment of chronic
SDH separately, whereas acute SDH may elevate the intracranial
pressure dramatically because of insufficient time for spatial
compensation of the brain and may require evacuation before
EBP. An individualized approach considering the risk and
benefits is needed to achieve a good outcome.
Conclusion
SIH is a distinct entity and requires a high index of suspicion
for diagnosis. The initial imaging findings may be normal or
subtle. A post‑contrast MRI should be included for evaluation
of headache and can clinch the diagnosis of SIH. Spinal MRI
should be done to demonstrate the site of the leak. The epidural
blood patch therapy is the most effective treatment of SIH. Most
of the SDHs associated with SIH do not require treatment.
Financial support and sponsorship
Nil.
Conflicts of  interest
There are no conflicts of interest.
 Shukla, et al.: Intracranial hypotension
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39. Park J‑Y, Ro Y‑J, Leem J‑G, Shin J‑W, Oh Y, Choi S‑S. Predictors
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 Original Article

Access this article online

Quick Response Code:
Shunt Implants – Past, Present and
Future
Dwarakanath Srinivas, Gaurav Tyagi, Gyani J Singh

Website: Abstract:
www.neurologyindia.com
Background: The treatment of hydrocephalus has evolved over centuries from being an enigma to the use of
DOI: complex bioprosthetics. Major developments have taken place in the past few decades in shunt hardware and
10.4103/0028-3886.332263 technology, with the use of complex flow regulating valves and biomaterials such as medical‑grade silicone
having revolutionized the management of hydrocephalus.
Objective: To discuss the evolution of shunts over the decades and how they will evolve in the future.
Material and Methods: In this article, we mention an overview of the evolution of shunt technology and
hardware from the prehistoric, pre‑shunt era to the modern shunt and a brief insight into the future of
hydrocephalus treatment. We review the history, development, and pioneers in shunt development and discuss
the various types and parts of a shunt system.
Conclusions: Shunts have been developed from the works of Galen and Hippocrates to the latest technologies using
in vivo flow biosensors, computational analysis of flow dynamics, and use of artificial intelligence. This has led to an
individualized and appropriate management that can be provided to even the most complex cases of hydrocephalus.
Key Words:
History of neurosurgery, hydrocephalus, medical‑grade silicone, shunt hardware, shunt history, shunt valves,
ventricular catheter, ventriculoperitoneal shunt

Key Message:
The technology behind shunts has been evolving and will continue to evolve over the coming years. Advances in
shunt technology have helped in difficult‑to‑treat hydrocephalous. In this article, we discuss the evolution of shunts
and the various types of shunts along with the differences in their structures as well as their indications and uses.

Historical Overview of the Pre‑Shunt Era end of the 19th century used a variety of materials
such as strands of catguts and gold tubes as

T he earliest mention of hydrocephalus

was found in the works of Galen and
Hippocrates.[1,2] In the 16th century, Vesalius
provided the first mention of the anatomical
basis of hydrocephalus and gross ventricular
anatomy. [3] Over the next two centuries,
further insights into the pathophysiology of
hydrocephalus were obtained but the treatment
options remained obscure.
In 1893, Jan Mikulicz‑Radecki performed
Department of the first reported ventricular CSF diversion
Neurosurgery, procedure.[1,3] He used a mass of glass wool in
NIMHANS, Bengaluru, the shape of a nail to puncture the ventricles
Karnataka, India and track the CSF into the subdural space in
a child [Figure 1]. This procedure halted the
Address for progression of hydrocephalus and thus paved
correspondence:
the way for future shunt developments. [3]
Dr. Dwarakanath Srinivas,
Buoyed by initial success, surgeons toward the
Department of
Neurosurgery, II
Floor, Faculty Block, This is an open access journal, and articles are distributed under the terms
NIMHANS, Hosur Road, of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0
Bengaluru ‑ 560 029, License, which allows others to remix, tweak, and build upon the work
Karnataka, India. non‑commercially, as long as appropriate credit is given and the new
creations are licensed under the identical terms.
E‑mail: dwarakaneuro@
yahoo.com For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com
ventriculo‑subdural shunts.[4‑6] In 1903, Nicolas
Senn reported the first recorded procedure
of ventriculo‑subcutaneous shunt by using a
perforated rubber tube [Figure 2].[3,5]
With the turn of the 20 th century, surgeons
started using variations in the hardware such as
glass tubes, split silver tubes, linen threads, and
even strips of omentum.[7‑9] Human or calf blood
vessels (veins) were also used as a conduit for
CSF diversion to the superior sagittal sinus, the
jugular vein, or the common facial veins. These
veins were oriented in such a way that their
valves would prevent backflow of blood and only
forward direction of the CSF flow.[5,6] Mechanical
obstruction or “stoppage” in the gold tube as a
cause of shunt malfunction was reported as early
as 1899.[5] The mechanical obstructions of these
early constructs and the incidence of infections
How to cite this article: Srinivas D, Tyagi G,
Singh GJ. Shunt Implants – Past, Present and Future.
Neurol India 2021;69:S463-70.
Submitted: 24‑Jun‑2021 Revised: 14-Oct-2021
Accepted: 22-Oct-2021 Published: 11-Dec-2021

© 2021 Neurology India, Neurological Society of India | Published by Wolters Kluwer - Medknow S463
 Srinivas, et al.: History of shunt
Figure 1: Artistic impression of gold-plated metal catheters with fixation attachment
used by Mikulicz’s as ventriculo-subarachnoid-subgaleal shunt, 1895
in the pre‑antibiotic era caused most of these efforts to fare
poorly in the long run.[6]
Characteristics of an Ideal Shunt
An ideal shunt would be one that mimics the normal brain’s
reabsorption of CSF into the venous system via the arachnoid
granulations, controls intracranial pressure, handles various
CSF changes, and reconstitutes the cerebral mantle. Currently,
shunts allow for a low resistance pathway for CSF diversion.[10]
The process of development and innovation in shunt design is
ongoing and we still have a long way to go for an ideal shunt
Anatomy of a Modern Shunt System
A commonly used modern shunt system is made up of the
following components:
1. An inflow (proximal or closer to the inflow site) catheter or
ventricular catheter (VC) that drains CSF from the ventricles
or the subarachnoid space.
2. A valve mechanism that regulates differential pressure or
controls flow through the shunt tubing.
3. An outflow  (distal or farther away from the inflow site)
catheter that runs under the skin and directs CSF from
the valve to the abdominal (or peritoneal) cavity, heart,
or other suitable drainage sites. While the inflow and the
outflow systems have had very little design changes except
the material used to manufacture them, most of the design
changes and innovations are based on valve design changes.
Early Beginnings and Evolution in Shunt
Development ‑ The Ventricular Catheter (VC) and
the Shunt Tubes
In 1939, Arne Torkildsen used a rubber catheter to divert CSF
from the lateral ventricles to the cisterna magna in cases of
aqueductal obstruction. The Torkildsen shunt was the most
notable precursor of a modern CSF diversion shunt [Figure 3].[11]
This shunt procedure (ventriculocisternostomy) was shown to
have good long‑term patency rates.[12] In 1951, Frank Nulsen and
Eugene Spitz reported the first successful ventriculo‑jugular
S464 Neurology India | Volume 69 | Supplement 2 | November-December 2021
Figure 2: The use of a perforated rubber tube as ventriculo-subgaleal shunt,
Nicholas Senn, 1903. Reproduced from Senn: Alienist Neurol 24:316–324, 1903.
Public Domain
shunt using a soft rubber catheter. This shunt is widely
regarded as the first modern completely internalized one‑way
flow regulating CSF diversion hardware.[13] Both these shunts
used rubber tubes for shunting CSF.[11,13]
In a bid to explore the possibilities of using better biomaterials
for ventricular CSF diversion, Franc D. Ingraham published
the safety of using a synthetic polymer, polyethylene, as a
ventricular catheter in 1947.[14] However, polyethylene was
found to be an unsatisfactory shunt material, with frequent
incidence of the distal end blockage by omentum or bowel in
the VPSs.[15] Robert Pudenz used polydimethylsiloxane (PDMS)
or silicone rubber for a ventriculoatrial shunt in 1957.[16]
His shunt system also incorporated a flushing device using
a diaphragmatic valve ensuring unidirectional flow. The
patency of both the ventricular and cardiac tubes could be
ascertained by compression and release of the dome of this
flushing device.[16] Silicone rubber became an extensively used
indwelling medical devices material in 1940s and 50s due to
its excellent bio‑inertness and elasticity.[6] In 1958, Richard
Ames placed the first silicone VPS and followed this report
with a series of 120 cases with promising results.[15] Eventually,
medical‑grade silicone (“Silastic,” Dow‑Corning Corporation)
tubing became an extremely popular material for shunts. These
simultaneous breakthroughs provided working materials that
were outstandingly biocompatible and resistant to mechanical
stress, an ideal complement to the new valve technology. In
the quest to solve the inherent problems of ventricular catheter
obstruction, especially the invasion of choroid plexus via
the catheter holes, Salomon Hakim in 1969 introduced novel
modifications (J‑shaped or “shepherd crook” and “finned type”)
in the shunt tips.[17] However, these systems proved to be of
limited benefits in the long run due to the complex and poor
functional designs.[6] Similar flanged catheter designs developed
to prevent catheter obstructions did not provide long‑term
successful outcomes and even proved to be dangerous while
doing revision causing brain tissue damage.[6,18,19]
Various studies evaluated the pathological basis of shunt catheter
obstruction in the 1980s.[20‑22] While various changes were made
 Srinivas, et al.: History of shunt
Figure 3: Artistic recreation of the original ventriculocisternostomy drawing by
Torkildsen, 1939
in the design of the catheter‑like floating‑air‑impregnated
catheter, selectively permeable mesh openings at the
tip and various other patents, all aimed at reducing the
blockage of the ventricular catheter;[6,23,24] only a few saw
the light of the day in terms of clinical use and popularity.
Similarly, new materials developed during this period were
polyhydroxyethylmethacrylate (pHEMA),[25] which based on its
strongly hydrophilic gel‑like surface showed initial promise of
less cell binding but could not live up to the already established
PDMS. Expanded polytetrafluoroethylene (e‑PTFE) or
commonly known as Gore‑tex biomaterials were found to have
good elasticity, low tissue reaction, and were safe as long‑term
implants. However, Gower et al.[26] in 1992 found that Gore‑tex
shunts were poor candidates to replace silicon elastomers
due to their “open‑cell structure” (internodal distance: 5 µm)
porosity allowing tissue ingrowth and mechanical obstruction.
In 1995, Medtronic Inc. introduced BioGlide, a VC coated with
polyvinylpyrrolidone (PVP), a hydrophilic substance which
when bound to the silicone surface creates a “water jacket” by
virtue of water absorption and prevents bacterial adherence
to shunt walls. However, its slippery surface became the cause
of its discontinuation in 2010 due to mechanical difficulties
in using shunt connectors and intracranial migrations.[22,27,28]
Most modern shunt catheters are made of silicone polymers
and are available in a straight configuration. Hole number, size,
shape, and spacing vary among the different manufacturers.
The length of a catheter varies from 15 to 23 cm.[29] The inner
diameters vary between 1.0 and 1.6 mm and outer diameters
between 2.1 and 3.2 mm.[30] The holes at the tip are arranged in
three to four rows and are equally spaced around the tube in
parallel or staggered configurations (4–8 holes in each row),[31]
the size of the holes range from 0.25 to 0.5 mm and many holes
may have a tapering or funnel shape toward the lumen.[32,33]
The major aim for continued research in shunt materials is to
limit cells and protein adhesions to the tube surface. In vitro and
preclinical studies suggests that variants of a nondegradable
hydrophilic polymer, polyethylene glycol, when coated on
shunt surface can reduce protein adsorption, astrocyte, and
macrophage attachment.[34] Catheter‑related infections can
also be reduced by the addition of silver nanoparticles to
such coating.[35] Recently, slit‑tip ventricular catheters have
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S465
been used for introducing a recently, fiberoptic endoscope
(Neuropen endoscope) have been used for introducing and
placing ventricular catheters like the Innervision catheter
(Medtronics), and Bactiseal endoscopic ventricular catheter
(BEVC; Codman). The endoscope doubles up as a stylet and
helps improvise proximal catheter placement.[29,36]
Distal catheter
The catheter length varies from 90 to 120 cm, depending on the
manufacturer. The internal diameter is between 0.7 and 1.3 mm,
and the external diameter is 2.1–2.5 mm. The catheters are made
of silicon polymers that can be barium‑impregnated to make
them radio‑opaque.[29] However, multiple studies have found
that barium reduces the elasticity of the shunt tubing, induces
calcifications, and makes them prone to fractures.[37‑39] The use
of distal‑end slit valves has been controversial and proved to
increase the chances of shunt block.[30,40] Current shunt tubes are
striped with barium compounds or have tantalum markings.[29]
Antibiotics‑impregnated shunt system
In 2001, the antibiotics‑impregnated shunt (AIS) was approved
by the FDA for commercial use (Bactiseal catheters, Codman
and Shurtleff, Inc).[41] These catheters were impregnated with
clindamycin and rifampicin into their silicone matrix. The
successful use of antibiotics impregnated shunts can be
attributed to the research started by Bayston and Milner in
1981, where they studied various antibiotics introduced at
different stages of silicone vulcanization.[42] Other prominent
antibiotics‑coated shunt systems are Ares (Medtronics) and
Silverline (Spiegelberg). While Ares contains the same rifampicin
and clindamycin combination in silicone, Silverline is coated
with an insoluble silver salt, which when gradually released
from the surface, shows strong anti‑bacterial properties. The
jury is still out on the efficacy of antibiotics impregnated shunts
in preventing shunt infections with conflicting reports in the
literature.[43‑46] However, recently the results of British Antibiotic
and Silver‑Impregnated Catheter for Ventriculoperitoneal
Shunts (BASICS) trial showed that in terms of shunt revisions
due to infections, AIS (2%) fared better than normal (6%) and
silver‑coated shunts (6%).[47,48]
In 2007, Medtronic’s Rivulet catheter was launched on the basis
of landmark work of Lin et al.,[49] who demonstrated the faulty
hole perforation patterns to be the cause of catheter obstruction
by computational fluid dynamics and experimental validation.
Rivulet catheter has four parallel rows of decreasing size
holes, with the distal holes being the largest. Computational
simulation studies proved the uniformity of flow distribution
of this design.[33,50] In 2008, Medtronic Inc. introduced extracted
unpolymerized oligomers silicone catheters for silicone‑allergic
patients.[51]
Shunt Valves
The valve is the most crucial part of the shunt system. Most
of the valves operate on the principle of change in differential
pressure, that is, the difference between the pressure of the
proximal catheter tip and the pressure of the drainage end. This
is the driving force and causes the shunt to open up, thereby
making the CSF flow.[10] Shunts have been classified depending
on various parameters. Based on pressure adjustability, there
are the following main types of shunt valves [Figure 4].
 Srinivas, et al.: History of shunt
Figure 4: The different types of shunt valves concepts used
Development of valves in the shunt systems
In 1907, Payr mentioned the use of a saphenous vein
ventriculo‑sagittal sinus shunt, with the venous valves
making it a regulated unidirectional flow shunt. [3] In the
1950s, engineers at the Massachusetts Institute of Technology
made the first magnetically operated valve for a shunt
construct. It was a magnetically sealed, gold‑plated ball
valve over a rubber‑polyethylene mixed shunt tube. This
valve was used in multiple cases in the Harvard Children’s
Hospital in Boston but was not pursued for long due to
complex construct, technical difficulties, and poor overall
outcomes.[3,52] The first successful use of a valved‑chamber
ventriculo‑caval shunt was mentioned by Eugen Spitz in 1949
at the Children’s Hospital (Philadelphia). The valve construct
was developed by Frank Nulsen by using a rubber pumping
chamber interspersed between two ball‑and‑cone valves with
helix springs in series [Figure 5].[13] In 1955, Robert Pudenz
and Ted Heyer (engineer) constructed a distal transverse slit
Teflon valve and implanted it into a ventriculoatrial shunt in
a child. This shunt worked successfully for 2 years.[53] In the
same year, John Holter, a machinist employed by Yale and
Town Lock Company, Philadelphia, made a dual silicone slit
valve mounted on a helix spring in a desperate attempt to
help his son who had myelomeningocele with hydrocephalus
and had multiple unsuccessful shunts. His valve was
successfully implanted in an atrial shunt by Eugene B. Spitz
and is still being used in modern times as the “Spitz–Holter”
valves.[54] Around the same time, W. Engelsman developed
a dual valve (ball valve combined with distal slit valve) in
Groningen, Netherlands, which was successfully implanted
by T. Sikkens.[55] The diaphragm valve design was patented
in 1960 by Rudi Schulte, a young watchmaker in Germany
working in association with Pudenz and Heyer.[3] The use of
a distal slit ventriculoperitoneal shunt was first reported by
Richard Ames in 1958.[15] A modified and improved version of
the VP shunt systems with distal slit valves was popularized
by Raimondi et al.[56] in the 1970s.
Modern valves
The main driving force in the evolution of the shunt systems
is the valve design and its role to manipulate the drainage of
CSF. The use of multistage or adjustable valves with anti‑siphon
devices is commonplace now. However, even with these
developments, there is no single valve design that is clearly
better than the rest for every hydrocephalus patient. At present,
Neurosurgeons can choose from more than 125 commercially
available valves. The following are the important categories of
valves used in modern shunt systems
Differential pressure valve
A differential pressure one‑way check‑valve mechanism is
one of the basic building blocks of any shunt system. The
S466 Neurology India | Volume 69 | Supplement 2 | November-December 2021
Figure 5: Nulsen and Spitz’s valved shunt in 1949. This valve is made of two ball-
valve units with an interposed pumping chamber.
fundamental of keeping the differential valve opening pressure
lower than the mean ventricular pressure for the CSF flow
across the valve is a basic misconception.[57] The CSF flow
depends upon the differential pressure across the valve and
not necessarily the absolute ICP. They are usually divided
into three criteria based on the CSF flow pressure resistance:
low (1–4 cm H2O), medium (4–8 cm H2O), and high (>8 cm
H2O).[10]
The most commonly used shunt system in India, Chhabra
shunt (Surgiwear), was first conceptualized and published in
1993 [Figure 6]. It contains a “Z‑flow” dual slit and spring valve
system and has three pressure variants (low, medium, and high
pressure).[58] Another notable contribution indigenous valve
developed in India was by Upadhyay et al.[59,60] Few examples
available DPVs are the Codman Hakim Programmable
and Precision Valves (DePuy Synthes, West Chester), Strata
Valve  (Medtronic, Minneapolis), and the pro‑GAV (Aesculap,
Center Valley), all of them using the ball‑spring valves.
Adjustable or programmable valves
Programmable valves contain a mechanism enabling precise
changes in the spring tension of a valve. These valves
incorporate a magnetic actuation of a rotor to induce changes
in the differential pressure across a valve to prevent the
development of under‑ or over‑drainage. Strictly speaking,
these valves are not truly programmable and are better
considered as merely adjustable valves.
The pioneering work in the development of the adjustable
valves was done by Kuffer and Strub in 1969; they developed
a piston‑type valve whose spring could be adjusted using a
screwdriver.[61] Later, a percutaneously controlled “on‑off”
type of shunt valve was designed by Portnoy in 1973.[62] In the
same year, S. Hakim reported his valve design that could be
magnetically calibrated over the skin [Figure 7].[63] Eventually,
the three‑level adjustable Sophy SU3 valve (60–160 mm H2O)
and later its expandable version SU8, Mini‑ 8 (30–200 mm H2O)
were developed by Cordis in collaboration with Hakim.[3,64]
However, the biggest drawback of these AVs is the cost as they
are 2–3 times more expensive than the fixed pressure valves.
Another concern especially with the early generation of the AVs
 Srinivas, et al.: History of shunt
Figure 6: Chhabra shunt system
is their MRI compatibility. However, recent Avs with locking
mechanisms fare better and are especially useful in patients
who are expected to undergo future MRI studies.
Flow‑regulated calves (FRV)
The basis of a FRV device function is the alteration in
hydrodynamic resistance to CSF flow with changes in its
pressure gradient. This mechanism maintains the flow rate
constant over a range of physiologic pressures (typically
8–30 cm H2O) and these valves are less likely to be associated
with siphoning and over‑drainage.[65,66] Orbis Sigma II valve is
the prototype of FRV shunts.[30] Also called pressure‑controlled
valves, these valves are made of a contoured synthetic ruby
flow‑control pin that fits inside a movable synthetic ruby
ring. FRVs produce a sigmoid‑shaped pressure‑flow curve
and behave as DPVs at the lower and higher spectrum of its
pressure spectrum by changes in the aperture. In the mid‑range
of pressure differentials, these valves maintain a constant flow
rate. One disadvantage of FRVs is the increased likelihood of
obstruction due to very small orifices.[32] Moreover, there is
no significant difference between the revision rates of FRV
vs DPV.[66]
Gravitational valves (GVs)
In 1975, Hakim patented the first “gravitational” valve.[63,67]
GVs are made to prohibit or reduce siphoning by increasing
opening pressure with the assistance of gravity when a patient
sits or stands. The GVs (or gravity‑actuated) typically have a
“ball‑in‑cone” (usually titanium) design, which acts as a simple
DPV in the recumbent position, coupled with a “gravitational
unit” that activates in the upright position. Thus, in the standing
or sitting position, the pressure of both the valves must be
overcome for CSF flow. The proper pressure valve selection
is dependent on the height of the patient. The commonly
used ones are the Integra Horizontal‑Vertical [H‑V] Lumbar
Valve (Integra LifeSciences Corporation, Plainsboro, NJ). The
Miethke ShuntAssistant (SA; Miethke) gravitational unit is
also available as a standalone ASD, and the ProSA (Aesculap,
Miethke) has an adjustable gravitational valve to be used in
growing children.[68‑71]
Broadly, shunt system development can be divided into
following generations based on their valves[10,29] [Table 1].
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S467
Figure 7: Diagrammatic representation of the first differential pressure valve used
by Solomon Hakim, 1973
Future Directions
An overall holistic approach for future VP shunt development
includes considering the fluid‑mechanical dynamics, hardware
design optimization, in vivo systematic fluid flow testing
through various catheter hole configurations, evaluating
ever‑evolving infection prevention measures, biocompatibility,
and surface properties of the materials used.[6]
Krishnan et al. [72,73] developed a noninvasive, wearable
skin‑mounted measurement platform that incorporates arrays
of thermal sensors and actuators for precise, continuous, or
intermittent measurements of flow through VP shunt systems
with rechargeable batteries and data transmission using Bluetooth
protocols. They successfully validated the ability of the device to
detect CSF flow rates and predict shunt failure on five patients.
ShuntCheck (Neuro Diagnostic Devices, Inc., Trevose,
Pennsylvania) is the only FDA‑approved device using a
thermal technique to detect CSF flow.[74] However, it detects
the presence or absence of flow but cannot quantify flow rate.
Thus, it cannot differentiate normal periods of shunt stasis from
shunt failure.[74,75] To address this problem, Qin et al.[75] tested
a novel in‑line flow sensor capable of monitoring quantitative
information about shunt CSF flow in an experimental swine
model with successful results.
Ventricular catheter obstruction accounts for 50%–80% of
shunt failure in newly inserted shunts in children.[50,76] The
development of novel catheter and shunt tubes with better
flow distribution and reduced shear stress of the catheter’s
holes based on parametric designs is an important step
toward resolving this problem.[33] Several models have been
successfully tested by means of computational fluid dynamics
with parameters such as the number of drainage segments, the
distances between them, the number and diameter of the holes
on each segment, and their relative angular position.[33,50,77]
Another important aspect is the shunt procedure itself and
technical as well as technological improvisations to achieve
overall shunt success. Patients with slit ventricles, abnormal
ventricular or cranial anatomy benefit from the use of radiopaque
 Srinivas, et al.: History of shunt
Table  1: A  brief classification overview of shunt valves development
First Generation Valves
Second Generation Valve
Fixed DPVs with anti‑siphon mechanisms
Programmable or adjustable DPVs
Third Generation Valves (Fixed DPV combined with hydrostatic valves to avoid CHPV with the Siphon guard‑CHPV‑SG, (Codman)
the siphon effect)
Fourth Generation Valves (Valves with programmable or adjustable ASDs)
DPV ‑ Differential Pressure Valves, ASD ‑ Anti‑Siphon Device
indicators (barium sulfate or tantalum) incorporated into the
shunt catheter, which helps in verifying correct tip positioning.
The use of intra‑catheter endoscopes (e.g. ShuntScope, Karl
Storz GmbH and Co.KG, Tuttlingen, Germany),[78,79] stereotaxy,
neuro‑navigation, or intra‑op imaging guidance for catheter
placement has become commonplace in most advanced
centers but is yet to become the norm.[6,36,80,81] Moreover, a clear
benefit of these technologies over the freehand technique using
anatomical landmarks has not been established.[82] With the use
of artificial intelligence and augmented reality the surgeon can
plan his trajectory with real‑time patient imaging and improve
outcomes. Recent studies have shown the use of smartphone
or mobile applications guidance as simple and safe methods
for correct shunt placement.[83,84]
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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S468 Neurology India | Volume 69 | Supplement 2 | November-December 2021
Basic fixed DPVs, with three pressure ranges (low,
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Orbis‑Sigma valve (Integra)
Delta valve
Dual switch valve (Miethke)
Gravity Activity valve (Integra)
Siphon X (Sophysa)
Shunt assistant (Aesculap)
Pressure Adjustable Sophy valve ‑ PAVS (Sophysa)
Sophysa‑Polaris valve (Sophysa)
Codman‑Hakim Programmable Valve ‑CHPV (Codman)
Strata NSC valve (Medtronic)
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 Review Article

Access this article online

Quick Response Code:
Techniques and Nuances in
Ventriculoperitoneal Shunt Surgery
Shibu V Pillai

Website: Abstract:
www.neurologyindia.com
Background: Ventriculoperitoneal shunt surgery (VPS) is a simple solution to the problem of hydrocephalus.
DOI: However, it is associated with significant complications. Meticulous attention to a variety of factors, techniques,
10.4103/0028-3886.332261 and nuances in VPS can reduce these complications.
Objective: To review the various techniques and nuances during the different stages of VPS.
Methods and Material: PubMed search for original and review articles dealing with various techniques used
during VPS.
Results: Thorough preoperative planning for VPS reduces operative time and complications. A standardized
shunt surgery protocol significantly reduces shunt infection. Good and appropriate surgical technique can
enhance the safety of the procedure. Anterior entry point is better than posterior entry point. Shunt tip should
be away from choroid plexus, but the exact location is not vital for shunt survival. Proper placement of the
shunt in the subgaleal and subcutaneous plane reduces wound and skin breakdown over the shunt. The trocar
and laparoscopic methods to access the peritoneum are associated with fewer distal obstructions compared
to mini‑laparotomy. Perioperative antibiotic prophylaxis, use of antibiotic‑impregnated shunts, and sutures
are proven techniques to reduce shunt infection.
Conclusions: Preoperative planning, a standardized shunt surgery protocol, good surgical technique, gentle
tissue handling, and short surgery duration are essential to reduce VPS complications. Specifically, use of
anterior entry point, correct tunneling of the shunt in the subgaleal and subcutaneous plane, appropriate
antibiotic prophylaxis, use of antibiotic‑impregnated shunts, and meticulous skin closure using antimicrobial
sutures can lead to a reduction in shunt malfunction and infection.
Key Words:
Complications, hydrocephalus, malfunction, techniques, treatment, ventriculoperitoneal shunt

Key Message:
Meticulous preoperative planning, a standardized shunt surgery protocol, good surgical technique, and
appropriate use of technology can reduce complications related to VPS.

Department of
Neurosurgery, Institute
of Neurosciences,
Mazumdar Shaw
Medical Center,
Narayana Health
City, Hosur Road,
Bangalore, Karnataka,
India
Address for
correspondence:
Dr. Shibu V Pillai,
Sr. Consultant
Neurosurgeon, Institute
of Neurosciences,
Mazumdar Shaw Medical
Center, Narayana
Health City, Hosur Road,
Bangalore – 560 099,
Karnataka, India.
E‑mail: drshibupillai@
gmail.com
V entriculoperitoneal shunt surgery (VPS)
is a simple solution to the problem of
hydrocephalus. However, it has been estimated
that almost half the shunts will be replaced by the
end of the second year.[1] Meticulous attention to
a variety of factors, techniques, and nuances in
VPS can reduce these complications. This review
discusses these techniques during the different
stages of VPS.
Principles of Planning VPS:
Patient factors
High levels of protein or cells in the CSF
could obstruct the proximal catheter or the
valve and thus cause shunt malfunction as
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demonstrated in patients with hydrocephalus
due to tuberculosis (TBMH) and CSF protein
levels of >200 mg/dl.[2,3] However, patients with
subarachnoid hemorrhage with hydrocephalus
show no demonstrable increase in the rate of
shunt obstruction. Thus, while there is no specific
criterion for CSF protein (except perhaps in
TBMH) or cells prior to insertion of a VP shunt,
it is prudent to rule out the possibility of CSF
infection if clinically indicated.
Patients who are emaciated or have extremely
low body weight and poor skin quality, especially
premature infants, are susceptible to skin
breakdown over a shunt and may benefit from
improving these factors prior to VPS.[4]
How to cite this article: Pillai SV. Techniques and
Nuances in Ventriculoperitoneal Shunt Surgery.
Neurol India 2021;69:S471-5.
Submitted: 22‑Jun‑2021 Revised: 29-Sep-2021
Accepted: 08-Oct-2016 Published: 11-Dec-2021

© 2021 Neurology India, Neurological Society of India | Published by Wolters Kluwer - Medknow S471
 Pillai: Techniques in VP Shunt Surgery
Technical factors
The surgeon should aim to complete the surgery in the
shortest possible time and hence should plan every step of the
procedure in advance. A standardized shunt surgery protocol
has been demonstrated to be a key factor in reducing shunt
infections.[5]
The choice of entry point, frontal or parietooccipital, depends
on size, anatomy and loculation of ventricles, and thickness
of cortical mantle. A thick cortical mantle reduces the risk of
cerebrospinal fluid (CSF) leak around the ventricular catheter.
Neuroendoscopy can help fenestrate multiloculated ventricles
into a single connected cavity into which a catheter can then be
guided under vision. The entry point in such a situation may
be different from a conventional entry point and can be aided
by neuronavigation.[6]
The ventricular catheter tip is positioned at a location where
it is least likely to be occluded by the collapsing ependyma
or choroid plexus. Tuli et al.[7] found a reduction in proximal
catheter obstruction with the catheter tip in the frontal
horn compared to the occipital horn. However, Whitehead
et al.[8] found that catheter location did not influence shunt
survival among 858 subjects. Moreover, anterior entry site,
compared to posterior, reduced shunt failure by approximately
one‑third (HR: 0.65, 95% CI: 0.51–0.83).
Thus, a careful study of the preoperative brain scan is essential
to decide the ventricular entry point and location of the tip
of the ventricular catheter. This information is then used to
measure the length of the ventricular catheter to be used
during surgery.
Operating room (OR) factors
VPS should be scheduled as the first operation in a clean
neurosurgical OR. Emergency VPS should be taken up only
in ORs used for clean surgeries. All equipment, instruments,
shunt hardware, and sutures required for VPS must be
available in OR prior to starting surgery. Entry into and exit
from OR should be restricted during VPS.
Hardware factors
No specific shunt design or valve type has been proven to be
more effective in preventing shunt obstruction.[9] Riva‑Cambrin
et al., [10] in a prospective study of 1026 primary shunt
placements, found that factors such as etiology, payer, center,
valve design, valve programmability, the use of ultrasound or
stereotactic guidance, and surgeon experience and volume had
no independent associations with shunt survival. However,
use of a programmable valve reduced proximal catheter
obstruction in one study involving 279 patients, perhaps by
preventing the collapse of ependyma around the openings of
the proximal catheter by reducing CSF drainage compared
to fixed type valves.[11] An anti‑siphon device can reduce
over‑drainage symptoms but may underdrain in the obese.[12]
An antibiotic‑impregnated shunt may be preferable, especially
in high‑risk patients such as newborns.[13‑15]
Abdominal factors
It is not necessary to reduce the length of the abdominal
catheter because the longer length of the distal catheter has
not been associated with an increased risk of distal catheter
S472 Neurology India | Volume 69 | Supplement 2 | November-December 2021
obstruction. Slit valves in the distal catheter, as opposed to a
single opening, increase the risk of distal catheter obstruction
by the omentum.[16,17]
Preoperative antisepsis
All patients are given 4% chlorhexidine body and head
wash a day before and on the day of VPS. Preoperative
antibiotics, usually third‑generation cephalosporins, are given
intravenously 30–60 minutes prior to skin incision.
Surgical Steps
Patient positioning
The right or nondominant side is preferred for the first VPS.
The patient is positioned supine with the head resting on a
doughnut roll and rotated contralaterally, and the body along
the edge of the operating table. A shoulder roll is placed under
the shoulders to provide a straight line between the thorax,
neck, and retro auricular region. [Figure 1]. Passage of the
shunt passer from the retro auricular region to the abdomen
is facilitated by ensuring that the mastoid process and clavicle
are in approximately the same horizontal plane.
Surgical site marking
1. Frontal entry site marking is a curvilinear incision
open posterolaterally (to avoid the incision crossing the
shunt hardware) and centered on the Kocher’s point,
which is located 1–2 cm anterior to the coronal suture
and approximately 3 cm lateral to the midline in the
mid‑pupillary line [Figure 2], or around the corner of
the anterior fontanelle in infants. A retro auricular jump
incision should also be marked. From this entry site, the
ventricular catheter can be placed in the frontal horn just
in front of the foramen of Monro, away from the choroid
plexus, by directing it along the line of intersection of two
planes, one toward the medial canthus of the ipsilateral
eye and the other toward the tragus of the ipsilateral ear.
In this line, the catheter will be perpendicular to the surface
of the brain and usually is in a good position at a depth of
approximately 5 cm. It should never extend beyond 7 cm
from the surface of the skull.
2. Parieto‑occipital entry site marking is a curvilinear incision
open infero‑laterally and centered on a point that is 4 cm
lateral to the midline, in a plane that is midway between
the orbito‑meatal plane (OMP) and the parallel vertex
Figure 1: Positioning of patient for shunt with posterior entry point and incision
marked based on orbitomeatal (OM) plane (red dotted line) and parallel vertex
plane (yellow dotted line). Trajectory of ventricular catheter (violet dotted line) is
midway between supraorbital plane (Blue dotted line which is parallel to OM plane)
and parallel vertex plane (yellow dotted line).
 Pillai: Techniques in VP Shunt Surgery
plane. [Figure 1]. This technique has the advantage of
accommodating all head sizes, unlike Frazier’s point (3 cm
lateral to the midline, 6 cm superior to the inion), Dandy’s
point (2 cm lateral to the midline and 3 cm above the inion)
or Keen’s point (3 cm above and 3 cm behind the pinna).
From this entry site, the ventricular catheter can be placed
in the frontal horn or in the occipital horn, both of which
are devoid of choroid plexus, by directing the catheter
toward the ipsilateral medial canthus in a plane midway
between the supraorbital plane (parallel to OMP through
supraorbital ridges) and the parallel vertex plane [Figure 1].
The length of the catheter can be measured on the brain scan
for both shunt tip locations and can be measured on the
patient as the distance from the burr hole to the Kocher’s
point for the frontal horn location.
3. The abdominal incision is made on a point centered about
2 cm lateral and 1 cm superior to the umbilicus. Staying
above the umbilicus reduces the risk of bladder injury.
Other incisions include subcostal or midline.[18]
4. All the incision sites are infiltrated with a combination of
lignocaine and adrenaline.
Surgical preparation
The operative field should be exposed from scalp incision
to abdomen. Hair at the incision sites should be clipped, not
shaved. Shaving the entire head is unnecessary. The surgical
field is prepared using 4% chlorhexidine scrub followed by
4% chlorhexidine tincture, which evaporates leaving the skin
dry. The entire operative field is then draped and covered with
an iodophor‑impregnated surgical incise drape. The surgical
team should double glove to reduce the risk of shunt infection.
Scalp incision
The curvilinear cranial incision is completed with the knife
held perpendicular to the skin surface because a wedged cut
becomes more difficult to close accurately. The incision should
go down through the galea into the loose areolar tissue above
the pericranium. In infants, skin closure is difficult without the
attached galea. The galea is separated from the pericranium
within the loose areolar plane. A hemostat is used to create a
small subgaleal pouch for the valve beyond the incision. This
pouch is then extended in the same plane as a tunnel, with the
Figure 2: Anterior entry point (Kocher’s point) for VP Shunt (black cross). Open
anterior fontanelle (black diamond).
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S473
help of a jump incision, if necessary, till the hemostat penetrates
the attachment of the nuchal fascia and enters the subcutaneous
plane of the neck.
Burr hole
A small circle of pericranium is cut with the monopolar cautery
and a burr hole slightly larger than the diameter of the catheter
is made at this spot.
Distal catheter insertion
The shunt passer is used to pass the distal catheter from head
to abdomen in the subcutaneous plane. The shunt passer can
be introduced either from the head end downwards or from
the abdominal end upwards [Figure 3]. The former ensures
that the shunt remains in the subgaleal plane and thus reduces
the chances of scalp breakdown over the shunt. Piercing the
nuchal fascia is easier from above. However, the risk of passing
below the clavicle and injuring the lung is greater if adequate
care is not taken. Once the shunt passer has reached the neck,
the skin must be lifted to guide the shunt passer above the
clavicle. Pushing down on the proximal end of the passer
greatly facilitates this maneuver. Once across the clavicle, the
shunt passer must be pushed medial to the breast bud to avoid
injuring it and is brought out through the abdominal incision.
The stylet of the shunt passer is then removed. After a change
of gloves, the shunt package is opened, a connector is anchored
to the valve end of the catheter by using a silk tie, the distal
slit valves if present are cut precisely in a straight line, the
shunt system is charged with Ringer’s Lactate and free flow
confirmed, and finally, the prepared distal catheter is passed
through the sheath, which is then removed. The catheter is
pulled down till the valve is sitting within the subgaleal pouch.
While the ventricle is being cannulated, the distal and proximal
exposed ends of the shunt must be kept covered with lint‑free
drapes. The shunt must always be handled with rubber‑shod
forceps and all contact with the skin must be avoided.
Ventricular access
A metal brain cannula in conjunction with monopolar cautery
is used to coagulate and fenestrate the dura and puncture the
cortex. The ventricular catheter with stylet in situ is passed
through the dural puncture in the direction discussed above.
The dura grips the ventricular catheter all around and reduces
peri‑tubal CSF leak. In the case of frontal entry, the stylet is
removed after entering the ventricle, marked by a small give
in the resistance. In the case of parieto‑occipital entry, while
targeting the frontal horn, the stylet should only be removed
after the tip has crossed the atrium of the lateral ventricle to
prevent the tip from sinking into the temporal horn. As the
stylet is being removed, the catheter is simultaneously pushed
ahead on the stylet to the desired depth, which has previously
been calculated to ensure the catheter tip is in the frontal horn
anterior to the choroid plexus. CSF is collected and sent for
analysis including cells, glucose, protein, Gram stain, and
culture. Avoid excessive egress of CSF. The assistant should
use a rubber shod hemostat to hold the catheter against the
skull to avoid inadvertent dislocation while the connection to
the distal catheter is being secured.
Silk ties are used to anchor the catheters to the connector
and to each other. It is important to ensure that the first
knot on the silk tie does not loosen while the second knot
 Pillai: Techniques in VP Shunt Surgery
Figure 3: Shunt passer tunneled subcutaneously from cranial to abdominal
incisions.
is being tied. Over‑tightening the tie can lead to the tie
cutting into the catheter. Care at this stage will prevent
catheter disconnection. The connector is then sutured to
the pericranium to prevent shunt migration. The distal end
of the abdominal catheter is pulled downwards to remove
any kinks in the catheter. Distal CSF flow is confirmed by
lowering the distal catheter or if necessary, by pumping or
aspirating the shunt chamber to dislodge any airlock that
may be blocking CSF flow.
Navigation or ultrasound guidance can be valuable in patients
with small or multiloculated ventricles and may reduce shunt
failure when used routinely in such cases.[19,20]
Peritoneal access
Peritoneal access is obtained using one of three techniques:
trocar, laparoscopic, and mini‑laparotomy.
Trocar
The bladder must be emptied using Crede’s maneuver prior
to using the trocar method to avoid injury to the bladder. With
the anterior abdominal wall lifted and held taut, the trocar is
inserted into a small abdominal incision and advanced with
controlled force in the direction of the contralateral iliac crest
till a “pop” is felt and heard as the trocar passes through the
anterior and posterior rectus sheaths into the peritoneal cavity.
The stylet is then removed and with the sheath held in place
by the assistant, the distal end of the abdominal catheter is
inserted into the peritoneal cavity. The catheter should enter
freely. If it tends to curl back, it is likely that the peritoneum has
not been punctured, and the above steps need to be repeated.
Once the catheter has been introduced into the peritoneum, the
sheath can be removed. Complication rates and distal shunt
obstruction with this technique are low.[21] This technique is
better avoided in obese adults.
Laparoscopic
The laparoscopic method is especially useful in obese patients
and in those with peritoneal scarring and adhesions, especially
following recovery from shunt malfunction due to abdominal
pseudocyst. It is associated with fewer distal obstructions
compared to mini‑laparotomy.[22,23] It is typically performed
by a general surgeon. Distal catheters laparoscopically placed
in the subdiaphragmatic space and anchored to the falciform
ligament have reduced rates of displacement and distal
malfunction.[24]
Mini laparotomy
This is the most used technique to access the peritoneal
cavity. The abdominal incision described earlier is widened
to approximately 3 cm in length and is deepened through the
S474 Neurology India | Volume 69 | Supplement 2 | November-December 2021
Figure 4: Confirming the entry into the peritoneum with free passage of a blunt
instrument (blue arrow) through the peritoneal opening while lifting the cut edges of
peritoneum and posterior rectus sheath with hemostats (yellow dots).
fat and Scarpa’s fascia to the anterior rectus sheath, which
is opened transversely. The vertical fibers of the underlying
rectus abdominis muscle are then visualized, and an artery
forceps is used to split the fibers of the muscle to reach the
posterior rectus sheath. Two small hemostat forceps are then
used to lift the posterior rectus sheath, and using a to‑and‑fro
motion alternating between the two forceps, the underlying
bowel falls away from the rectus sheath, which is then
incised transversely. Sometimes, this simultaneously opens
the underlying transversalis fascia and the peritoneum. This
is confirmed by the free passage of a blunt instrument into
the peritoneal cavity [Figure 4]. If the instrument encounters
resistance, it means that the peritoneum has not been opened.
The peritoneum is then visualized and opened using the same
technique as for the posterior rectus sheath. After ensuring
the abdominal catheter passes freely and completely into the
peritoneum, the fascia is closed in layers around the shunt
tube.
Other sites of incision for the mini‑laparotomy include the
lateral subcostal incision and the midline vertical. The former
enters the peritoneal space over the liver and thus minimizes
the risk of bowel perforation but involves passing through
three layers of muscle. The latter incision has the advantage
that it goes through the avascular linea alba.
Closure
The operative sites are irrigated with amikacin in Ringer’s
lactate solution. Both the incisions are closed in layers using
antimicrobial sutures.[25] Subcuticular closure is preferred.
Post‑Surgical Care
Perioperative antibiotics are recommended but the evidence for
their route of use and duration of use is unclear. Use beyond
24 hours is unlikely to be beneficial.[26] Adequate postoperative
analgesia is important. The head should be kept elevated by
30°–45°. Dressings should not be removed for 48 hours after
the procedure, and after that, the hair can be washed and the
wound left open.
 Pillai: Techniques in VP Shunt Surgery
Conclusions
Preoperative planning, a standardized shunt surgery protocol,
good surgical technique, gentle tissue handling, and short
surgery duration are essential to reduce VPS complications.
Specifically, use of anterior entry point, correct tunneling of the
shunt in the subgaleal and subcutaneous plane, appropriate
antibiotic prophylaxis, use of antibiotic‑impregnated shunts,
and meticulous skin closure using antimicrobial sutures can
lead to a reduction in shunt malfunction and infection.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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Rozzelle CJ, Tamber MS, et al. Ventricular catheter entry site and
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11. McGirt MJ, Buck DW II, Sciubba D, Woodworth GF, Carson B,
Weingart J, et al. Adjustable vs set‑pressure valves decrease the
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 Review Article

Access this article online

Quick Response Code:
A Brief Review of Ventriculoatrial and
Ventriculopleural Shunts
Thirumal Yerragunta, Vijaya Sekhar Manda1, Vamshi Krishna Yerramneni,
Ram Nath Reddy Kanala 

Website:
www.neurologyindia.com
Abstract:
DOI: Introduction: Alternate approaches such as ventriculoatrial (VA) or ventriculopleural (VPL) procedures still
10.4103/0028-3886.332248 have a place in the surgical armamentarium for patients with recurrent ventriculoperitoneal (VP) shunt failures
related to defective absorption, infections, or frequent malfunctions.
Methods: We reviewed the literature and our experience with these techniques, and offered suggestions
for safely performing these operations. Historical perspectives were also included to facilitate an improved
understanding of the technical developments.
Results: Our findings and the available medical literature suggest VA and VPL options are safe and effective
alternatives for managing the complex patient with hydrocephalus. Potential issues and complications were
discussed along the technical advances for a safer operation.
Conclusion: The VA and VPL options should be considered for patients with recurrent VP shunt issues. They
are safe and effective options for managing complex hydrocephalus patients.
Key Words:
Atruim, complex hydrocephalus, pleural space, shunt complications, ventriculoatrial shunt, ventriculopleural
shunt

Key Message:
Ventriculoatrial and Ventriculopleural shunts remain effective alternatives for patients with recurrent
ventriculoperitoneal shunt failures. Percutaneous insertion techniques (Seldinger method or trocar insertion)
have refined the operations, and these alternative shunt procedures should be considered in managing
complex hydrocephalus.

Department of
A lthough ventriculoperitoneal (VP)
shunts have remained the mainstay of
hydrocephalus management, alternate options
are excellent alternate sites for patients with
abdominal issues, poor absorption,[1,2] or other
reasons such as peritoneal tuberculosis,[3] where
Neurosurgery , are sometimes necessary. Recent technological the peritoneum cannot be utilized as a primary
Nizam’s Institute of advances have made VP shunts more durable and option for distal shunt placement.
Medical Sciences, consequently, experience with the less commonly
Hyderabad, Telangana used shunts is becoming scarce. Alternate Brief history and evolution of the VA shunt
and Department of approaches such as ventriculoatrial (VA) or The neurosurgery historical review suggests that
Neurosurgery, King ventriculopleural (VPL) procedures still have a few other surgical procedures have undergone
George Medical place in the surgical armamentarium, and their so many modifications as the CSF diversion
College, Maharani use will be reviewed here. technique.[4] The concept of VA Shunt to divert
Peta, Visakhapatnam, CSF into venous or lymphatic system was first
1
Department of Historically, VA shunts have always enjoyed proposed by Gartner,[5] almost a decade before
Neurosurgery, good functional outcomes, although they the first VP shunt in 1905 by Kaush. Pudenz
Maharani Peta , required multiple revisions due to growth in observed in his animal experiments that placing
Visakhapatnam, children and other complications. The chronic the distal catheter tip in internal jugular vein (IJV)
Andhra Pradesh, India low pressure in the atrium along with cardiac or superior vena cava (SVC) resulted in catheter
activity somehow improves a shunt function blockage and vein occlusion due to capsule
Address for and many patients have identified long‑term formation at the tip.[6] Thus, the placement of
correspondence:
benefits by this physiologic phenomenon. These
Dr. Thirumal Yerragunta,
Associate Professor of How to cite this article: Yerragunta T, Manda VS,
Neurosurgery, Nizam’s This is an open access journal, and articles are distributed under the terms Yerramneni VK, Reddy Kanala RN. A Brief Review of
Institute of Medical of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 Ventriculoatrial and Ventriculopleural Shunts. Neurol
Sciences, Hyderabad, License, which allows others to remix, tweak, and build upon the work India 2021;69:S476-80.
Telangana, India. non‑commercially, as long as appropriate credit is given and the new
creations are licensed under the identical terms. Submitted: 20‑Oct‑2021 Revised: 27-Oct-2021
E‑mail: drtirumal@gmail.
Accepted: 29‑Oct‑2021 Published: 11-Dec-2021
com For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com

S476 © 2021 Neurology India, Neurological Society of India | Published by Wolters Kluwer - Medknow
 Yerragunta, et al.: Ventriculoatrial and pleural shunt
catheter tip at right atrium had been standardized and in
1957, Pudenz introduced the VA shunt technique.[7] To access
the right atrium, although various routes like external jugular
vein,[8] transverse sinus,[9] or subclavian vein[10] had been
described, the IJV became the choice for many surgeons due
to infrequent complications.
The percutaneous access to the IJV for VA shunt insertion was
first proposed by Sorge et al.[11] who used special instruments
for the Seldinger’s technique. Other surgeons later performed
this procedure using various available sheaths and catheters to
cannulate the IJV or subclavian vein to place the distal shunt
tube into the right atrium.[10,12,13]
Preoperative evaluation
As the distal drainage of CSF is into the heart via the venous
system, it is imperative that the patency of IJV and SVC be
properly assessed preoperatively. Patients with a history of
previous or current central venous line placement, history
of pulmonary hypertension, or inherent cardiac abnormality
should be evaluated with color doppler and 2D Echo.
Surgical considerations
The IJC vein is preferred over SCV due to anatomic advantage
and fewer complications. Due to favorable venous anatomy,
the right IJV is preferred over left unless contraindicated. Only
the distal shunt insertion procedure will be reviewed here.
The patient is positioned supine, preferably on a radiolucent
table with head turned to opposite side with mild extension
of neck. Surgeon, assistant, and scrub nurse are ergonomically
positioned to allow the fluoroscope during the placement of
distal catheter.
For a VA Shunt, the distal catheter can be introduced into
right atrium via an open method with IJV exposure or more
commonly by using the percutaneous Seldinger’s technique.
The original technique is suggested using the facial vein
if large enough and easily accessible to insert the distal
tubing (alternatively the IJV can be used, especially in small
children). In an open method, the IJV is exposed after a vertical
incision at the medial side of sternocleidomastoid muscle and
catheter introduced after a small stab incision into the IJV. The
distal catheter is then secured to the vein using a 6‑0 Prolene
suture in a purse string fashion.
In the percutaneous method, the right IJV is punctured at
the cricoid level with an introducer needle at 30–40° angle
to skin targeting the ipsilateral nipple. This is done while
simultaneously palpating the carotid at superior apex of
the sternocleidomastoid (SCM) muscle triangle. In case of
altered anatomy due to previous surgeries or irradiation,
ultrasound guidance is advised. The guidewire is inserted
through the needle to approximately T6–T8 vertebral level
(which corresponds to mid atrium) under fluoroscopic
guidance with close monitoring of ECG or trans esophageal
echocardiogram when available. A stab wound is made for the
dilators. The introducer needle removed keeping the guide wire
in situ. The serial dilators of the hemodialysis catheter are used
to enlarge the track that is prepared over the guide wire. The
dilator is removed, keeping the guide wire in place, and lastly,
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S477
a peel‑away sheath of 10‑12 F (Mahurkar Chronic Carbothane
catheter kit, Covidien, Mansfield, Massachusetts, United States)
size is introduced over the previous dilator. The guide wire
and the inner dilator are removed, leaving an open channel for
passage of the distal catheter (brought to this site from above).
The catheter is measured and cut to the approximate length for
reaching the D6 spinal level. A heparin flush can be given in
to the IJV before placement of the catheter. The distal tube is
gently passed into the peel‑away sheath with a simultaneous
fluoroscopy and ECG tracking. After confirmation of proper
distal tip placement, the outer sheath is gently peeled off while
securing the catheter in situ.
Sometimes, peel‑away sheaths are not available or the dilators
are of a smaller diameter that will not allow passage of the
distal catheter (i.e., Chabbra shunt (Surgiwear, India) that has
an outer diameter of 7.5 F). In such instances, the distal catheter
tube is measured and divided from the neck stab wound and
advanced into the atrium over the stand alone guide wire
(after dilator removal). The proximal and distal tubing are
finally joined over a connector and secured.
The final position of the tube is confirmed again with the
fluoroscope after repositioning the neck to the neutral
position. If the catheter tip is not visible properly, a contrast
agent can be administered via the catheter to improve
visualization.
Final hemostasis is verified and the wounds are closed, with
pressure padding applied over the cervical stab wound for a
day.
Postoperative evaluation
A chest x‑ray should be done postoperatively to document the
position of the catheter tip and to rule out a pneumothorax.
Postoperatively, ECG should be monitored closely for 1–2 days
for cardiac arrythmias and if they persistently occur, the distal
catheter can be withdrawn by 1–2 cm.
Complications
Complications after a VA shunt operation may be early or
delayed [Table 1]. Early complications can be arrhythmias,
pneumothorax, thrombosis, endocarditis, or pulmonary
thromboembolism.[14] Venous thrombosis usually responds
to low molecular weight heparin with or without the need
for shunt revision. Sepsis with endocarditis needs urgent
removal of the shunt system with appropriate culture sensitive
antibiotics with simultaneous external ventricular drainage.
Pulmonary thromboembolism is managed with low molecular
weight heparin after removal of the shunt.
Table 1: Early and late complications after a VA
shunt operation
Complications of VA Shunt
Early complications Delayed complications
Bleeding Outgrowing the shunt
Arrhythmias Shunt nephritis
Venous thrombosis Shunt occlusion
Endocarditis and sepsis Pulmonary thromboembolism
Pneumothorax Delayed intracranial hemorrhage
Wound infection Cor Pulmonale
 Yerragunta, et al.: Ventriculoatrial and pleural shunt
Delayed complications such as shunt tip migration in
growing children, shunt nephritis, delayed shunt occlusion
due to venous thrombosis or shunt tip occlusion, or chronic
pulmonary micro thromboembolism leading to life‑threatening
cor pulmonale.[15]
Shunt migration is one of the most common complications
in VA shunt and requiring an elective revision in more than
two‑third of the patients.[16] In children where VA shunt is
done before the cessation of growth spurt, chest x‑ray every
2–3  years may give us an early clue of shunt migration.
Shunt‑related glomerulonephritis is a rare, reversible immune
complex‑mediated infection leading to end‑stage renal disease.
This complication may occur within a month or be diagnosed
several decades later. Most patients will require antibiotic
therapy with shunt removal, and will generally have a
favorable outcome.[17,18] VA Shunt malfunction due to any of the
above causes will present with features of raised intracranial
pressure (ICP) and should be immediately noted and the cause
must be addressed.
The ventriculopleural shunt
The pleural cavity is an excellent option for patients who are
otherwise not good candidates for peritoneal or other distal
placements.[19] Although rarely used today, this operation offers
long‑term successful shunt function for many individuals, and
can be considered in children as young as 4–5 years of age. As
such, the neurosurgeon should familiarize himself or herself with
this technique and its nuances. Interestingly, the pleural cavity
also has a vacuum that allows improved shunt function in certain
cases. In addition, this cavity can accommodate extra tubing to
allow for a child’s growth.[20] Most patients tolerate a shunt within
the pleural space, and the large surface usually accommodates
the typical amount of CSF output in the hydrocephalic patient
(after the initial period of adjustment to the new challenge).
Brief history and evolution of VPL shunt
Ventriculopleural (VPL) shunting for hydrocephalus was first
introduced by Heile in 1914.[21,22] Hoffman, et al.[20] (1983) gave
support to this option and provided a nice historical review,
citing an initial attempt to drain CSF into the thoracic duct and
pleural cavity by Ingraham and Sears. They chronicled other
refinements by Ransohoff in 1954 and 1963, and Fein and Rovit,
Venes (1979). With the advent of the VA shunt, this technique
has lost some of its original popularity, although it remains
an excellent option for challenging cases. The worldwide
experience with VPL is limited in the literature but historically
this technique has enjoyed a positive benefit for the patients
in most instances.[22‑25]
At King George Hospital, part of Andhra Medical College,
Visakhapatnam, India (a tertiary care facility), only one VPL
shunt was performed out of 112 shunt operations over the past
3 years. This speaks to the rarity of this surgical option in most
centers and is offered for a patient who has exhausted most
other options for effective shunting.
Technique
The proximal insertion technique is the same as others, and
entering the pleural cavity is most easily done using a trocar. An
open technique is also feasible but may be more cumbersome
and time‑consuming.
S478 Neurology India | Volume 69 | Supplement 2 | November-December 2021
The pleural space is accessed after distal tunneling using a
stabbing session and a trocar is used above the rib (to avoid
the vascular and neural bundle on the lower side). The
anesthesiologist requested not to ventilate the patient during
penetration, and the area is continuously irrigated so as to
avoid a large pneumothorax. A positive pressure Valsalva
maneuver is performed by the anesthesia team to expel any
excess air from the pleural cavity prior to removing the trocar.
Approximately 25–30 cm of distal tubing can be easily inserted
into the pleural cavity even in small children (this length helps
keep the shunt in the pleural space, decreasing the possibility
of external migration).
An immediate postoperative x‑ray is obtained to assess the
tube placement and free air in the pleural cavity. The patient
will need to be followed up for several days for clinical issues
(i.e., breathing difficulties) and radiographic deterioration
(i.e., increasing plural effusion). The amount of pleural fluid
buildup typically increases over the next few days prior to
improved absorption.
Not every patient can readily absorb CSF output and the cavity
needs to be ‘primed’ over a few weeks. During the initial
phases of placement, the patient needs to observed closely for
enlarging pleural effusions that sometimes require periodic
thoracentesis. The patient will almost always maintain a small
amount of pleural fluid that can be verified by x‑rays, especially
in the lateral decubitus position.
Rarely, the patient cannot tolerate the device and another
distal insertion site might need to be considered. Pneumonia
occurring close to the catheter may extend into the pleural
space, leading to pleurisy or fibrosis. Loculated fluid collections
may occur, causing issues with fluid absorption or symptoms
of shunt malfunction.[26,27]
Surgical consideration (open technique)
An incision is made over sixth intercostal space and the
pleura is entered at the upper border of the rib to avoid injury
to neurovascular bundles that lie inferiorly. The intercostal
muscles are dissected with a curved hemostat and the pleura
is exposed. Positive pressure is performed by the anesthetist
during pleural penetration and distal shunt insertion. Entry
into the chest cavity is accomplished with a small mosquito
hemostat along with the distal shunt tubing.
Approximately 25–30  cm of tubing is gently and freely
advanced into the pleural cavity while the area is irrigated to
minimize air entry. The wounds are closed after confirming that
there are no air or CSF leaks. Rarely, additional deep sutures
are required if a pleural opening is made.
An immediate 2‑view chest x‑rays are taken to asses distal tube
placement and amount of free air in the chest cavity. Serial
films are required  (using lateral decubitus positioning) to
evaluate CSF accumulation and the patient is followed closely
for respiratory issues. Enlarging pleural effusions sometimes
require periodic thoracentesis.
Complications
Complications after VPL shunt surgery include infections, CSF
over drainage, catheter obstruction, distal catheter retraction,
 Yerragunta, et al.: Ventriculoatrial and pleural shunt
Table 2: Early and late complications after a VPL
shunt operation
Complications of VPL Shunts
Early complications Delayed complications
Bleeding Pleural effusion
Pneumothorax Shunt nephritis
Wound infection Distal occlusion
Pleural effusion Fluid loculation
Outgrowing the shunt
and symptomatic and asymptomatic pleural effusions Table 2.
In rare instances, loculations or focal abscesses/empyema may
occur after a bout of pneumonia infecting the foreign body
in the pleural space. The possibility of scarring and pleurisy
with a pain syndrome may occur, but relatively unusual.[15,23,22]
Key points regarding VPL shunts
1. The pleural cavity should be without any fibrosis or
adhesions and the lung should be free from any underlying
pathologies.
2. Children with small chest and decreased pleural cavity may
not accommodate or absorb CSF adequately. The patient
should be above 5 years of age having good volume of
pleural cavity.
3. Due to the negative pleural pressure, there may be over
drainage of CSF resulting either slit ventricle syndrome or
large pleural effusion.[28] Lower end with anti‑syphon valve
may overcome this.[29]
4. The distal tubing in the pleural cavity may irritate the
pleura and produce pain. There are no studies regarding
ideal tubing length, although it is known that short 9
(less than 10 cm) may migrate out of the pleural space.
5. The patients must be thoroughly screened pre‑  and
post‑operatively for pulmonary and pleural reserves.
Inadvertent injury to lung should be evaluated with post
procedure chest x‑rays.
6. Entry into pleural space by trocar insertions is an alternative
for open procedure 2.[30,31]
The failure rates may be equal as that of VP shunts, because
similar mechanisms causing inadequate absorption may play
a role in both sites, resulting in persistent pleural effusions
and causing symptoms. In such cases, pleural shunt removal
may be necessary.
Discussion and Conclusion
Among the various time‑tested procedures for CSF diversion,
the VP shunt remains the gold standard. In select cases
and because of technical advances, the minimally invasive
endoscopic third ventriculostomy (ETV) operation has emerged
as a better alternative. However, in few situations where both
VP and ETV procedures have failed, other options need to be
explored to minimize the morbidity. For such patients, VA
and VPL shunts remain an excellent alternative (along with
others such as ventriculo‑subgaleal or ventriculo‑gall bladder
options).
The VA shunts are considered an excellent alternate for patients
with abdominal issues like impaired absorption, peritoneal
tuberculosis, and the like. Improved shunt function has made
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S479
this a reliable alternative for many surgeons. However, the
major drawbacks of infection, chronic lung/kidney issues or
multiple revisions in the pediatric population remain as major
concerns of this procedure.
The VPL shunts are an effective alternative to overcome some of
these challenges. The revision rate is low and for the most part,
the operation is similar to a conventional shunt. Only the distal
end insertion into pleural cavity by a trocar or conventional
open method are different. This is relatively a simple technique,
but the surgeon should be careful about lung contusion or
development of a large pneumothorax. Patients often require
to improve CSF absorption from the pleural space, and in some
cases become symptomatic with respiratory issues.
In spite of few such challenges, the VA and VPL shunts still
remain effective alternatives for patients with recurrent VP
shunt failures related to defective absorption, infections, or
frequent malfunctions. Especially with technical advances of
percutaneous insertion (Seldinger method for VA and trocar
insertion for VPL), the standardized procedures have become
less cumbersome and more effective. They should be added
to the surgeon’s options for managing patients with complex
hydrocephalus.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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10. Evangelos D, Dimitrios G, Georgios S, Nikolaos E, Filippos P,
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[Percutaneous ventriculoatrial shunt: Experience with 179 cases].
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 Review Article
Access this article online
Quick Response Code:
Website:
www.neurologyindia.com
DOI:
10.4103/0028-3886.332265
Department
Neurosurgery,
Superspeciality
Hospital, NSCB Medical
College, Jabalpur,
Madhya Pradesh, India
Address for
correspondence:
Prof. Yad R Yadav,
Department of
Neurosurgery, 4th floor,
Superspeciality
Hospital, NSCB Medical
College, Jabalpur,
Madhya Pradesh, India.
E‑mail: yadavyrns@gmail.
com
© 2021 Neurology India, Neurological Society of India | Published by Wolters Kluwer - Medknow S481
Lumboperitoneal Shunts ‑ Patient
Selection, Technique, and Complication
Avoidance: An Experience of 426 Cases
Mallika Sinha, Jitin Bajaj, Ambuj Kumar, Ketan Hedaoo, Sandeep Sharma,
Kamesh Konchada, Shailendra Ratre, Vijay S Parihar, Narayan M Swamy,
Yad R Yadav
Abstract:
Background: Lumboperitoneal shunt is a known procedure for communicating hydrocephalus. Being an
extracranial procedure, it can also be utilized in normal‑sized ventricles.
Objective: To report our experience of lumboperitoneal shunt done with a minimal follow‑up of 12 months
with an emphasis on patient selection, technique, and complication avoidance.
Methods: This was a retrospective analysis of patients who underwent LP shunt during October 2014–October
2019 at the authors’ institute. Inclusion criteria were patients with communicating hydrocephalus due to
tubercular meningitis, normal pressure hydrocephalus, idiopathic intracranial hypertension, and postoperative
refractory cerebrospinal fluid leaks. Data were collected for demographics, Glasgow coma scale and Glasgow
outcome scale, vision, gait, memory, urinary incontinence, failed attempts, and complications.
Results: A total of 426 patients underwent the LP shunt procedure. The commonest indication was tubercular
meningitis followed by idiopathic intracranial hypertension and normal pressure hydrocephalus. Age ranged from
16 to 72 years. There were 255 male and 171 female patients. The mean follow‑up was 41 ± 8 months. Overall,
301 patients (70.6%) had neurological improvement. Shunt‑related complications occurred in 112 (26.29%)
patients, of which shunt block was the commonest. Other complications were infection in 17 (3.9%) patients
and extrusion in four (0.9%) patients. Transient postural headache was seen in 46 (10.7%) patients, which
gradually improved.
Conclusion: Lumboperitoneal shunt was found to be a safe and effective treatment in appropriately selected
communicating hydrocephalus patients. A meticulous technique reduces the complication rate.
Key Words:
Cerebrospinal fluid shunts, hydrocephalus, idiopathic intracranial hypertension, normal pressure hydrocephalus,
postoperative complications, shuntography, tubercular meningitis
Key Message:
Lumboperitoneal shunt is a safe and effective treatment for varied causes of communicating hydrocephalus.
Tubercular meningitis, idiopathic intracranial hypertension, normal pressure hydrocephalus, and postoperative
cranial and spinal cerebrospinal fluid leaks are appropriate indications. A meticulous technique reduces the
complication rate.
L umboperitoneal (LP) shunt is an effective
and safe procedure for communicating
hydrocephalus[1,2] and in some non‑hydrocephalic
difficulty in function assessment.[2] Currently,
the indications of LP shunt include idiopathic
intracranial hypertension (IIH), communicating
conditions. [2] LP shunt has a distinctive hydrocephalus due to tubercular meningitis (TBM)
advantage of being an extracranial procedure, or other chronic infections, hydrocephalus due
thus reducing the risk of seizures, intracranial to SAH, post‑traumatic or post‑craniotomy
hematoma, subdural hematoma, meningitis, persistent CSF leak, pseudo‑meningocele, normal
ventriculitis, and requirement of postoperative pressure hydrocephalus (NPH), and slit ventricle
antiepileptic prophylaxis. [2–5] Associated
drawbacks are orthostatic over‑drainage and
How to cite this article: Sinha M, Bajaj J,
Kumar A, Hedaoo K, Sharma S, Konchada K, et al.
This is an open access journal, and articles are distributed under the terms Lumboperitoneal Shunts - Patient Selection, Technique,
of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 and Complication Avoidance: An Experience of 426
License, which allows others to remix, tweak, and build upon the work Cases. Neurol India 2021;69:S481-7.
non‑commercially, as long as appropriate credit is given and the new
creations are licensed under the identical terms. Submitted: 26‑Jun‑2021 Revised: 27‑Sep‑2021
Accepted: 09‑Oct‑2021 Published: 11-Dec-2021
For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com
 Sinha, et al.: Lumboperitoneal shunts
syndrome.[1,6–11] Persistent raised intracranial pressure (ICP)
after surgical repair in spontaneous rhinorrhea are also suitable
cases for LP shunt. Patients with growing skull fracture with
extensive dural defects in the cranial base or across venous
sinuses are also suitable candidates for LP shunt.[12,13] Despite
the high reported incidence of shunt obstruction and seizure
disorder, ventriculoperitoneal (VP) shunt is extensively used
in all types of hydrocephalus.[1,3,14] Many surgeons are hesitant
in using LP shunt due to high complication rates reported in a
few of the earlier series and difficulty in assessing function.[15]
Here, we have shared our experience of LP shunt done in the
last 5 years with a minimal follow‑up of 12 months.
Materials and Methods
This is a retrospective analysis of patients who underwent
LP shunt during the period from October 2014 to October
2019 in the department of Neurosurgery, NSCB Medical
College, Jabalpur. Institutional review board permission was
taken to collect the data. Inclusion criteria were patients with
communicating hydrocephalus due to tubercular meningitis,
normal pressure hydrocephalus, idiopathic intracranial
hypertension, and patients with postoperative CSF leaks who
failed on conservative management. Patients with persistent
increased ICP after rhinorrhea repair were also considered
for LP shunt. Communicating hydrocephalus was defined
as enlargement of all four ventricles and basal cisterns.
Patients with obstructive hydrocephalus and lumbar canal
stenosis (LCS) were excluded. All patients underwent a detailed
history, clinical examination, visual and fundus assessment,
preoperative computed tomography (CT) brain to determine
the type of hydrocephalus, and lumbar X‑rays to rule out LCS.
A diagnostic lumbar puncture for analysis and a therapeutic
lumbar puncture in cases of NPH by using the 30 ml CSF tap
test and assessing the opening pressure, improvement in gait,
cognition, and urinary incontinence were done.[16] The IIH
was assessed by recording raised opening pressure of >25 cm
H2O. Acetazolamide or mannitol if given was stopped after the
surgery. Antitubercular therapy was continued.
Data were collected for demographics, comorbid illness,
indications, pre and postoperative neurological examination in
the form of Glasgow coma scale (GCS) and Glasgow outcome
scale (GOS), vision, gait, memory, and urinary incontinence.
The follow‑up was done either in the outpatient department
or telephonically at 45 days, 3 months, 6 months, 1 year, and
then yearly. The follow‑up ranged from 12 to 72 months, with
a mean of 41 ± 8 months. CT brain was performed either at
45 days postoperatively or earlier if the patient fails to improve
or deteriorates. Routine magnetic resonance imaging was not
performed. Complications were noted in the form of failed
needle insertion, shunt fracture, shunt block, shunt revisions,
infection, postural headaches, over‑drainage, CSF leaks,
seizures, and intracranial hematoma.
Shunt assembly details [Figure 1]
The Chhabra LP shunt (Surgiwear, Shahjahanpur, UP, India)
without chamber was used in all cases. The lumbar end of
the catheter is radio‑opaque having multiple small holes with
markings at 5, 10, and 15 cm, has an inner diameter of 0.7 mm,
and an outer diameter of 1.5 mm. The peritoneal end has an
S482 Neurology India | Volume 69 | Supplement 2 | November-December 2021
a b
c
Figure 1: (a) Patient in the left lateral position. (b) The Tuohy needle being inserted
to put the thecal end. The peritoneal end has already been passed subcutaneously
and secured anteriorly. (c) Components of the lumboperitoneal shunt
outer diameter of 2.5 mm and an inner diameter of 1.3 mm. It
has one pair of vertical slit valves and is also radio‑opaque.
A metal connector connects the two ends. Other shunts are
available commercially with programmable/adjustable valves
and with a reservoir in multiple combinations, which can be
chosen according to the patient’s symptoms, etiology, opening
pressure, and to correct the over‑drainage problem.
Assessment of LP shunt function
LP shunt patency can be assessed by LP shuntography
if there is a clinical deterioration or nonresolution of
symptoms.[2] Iohexol contrast is instilled intrathecally, and
sequential images of abdomen and head can be taken to see
flow through the shunt. In shunts with a reservoir, tapping
and flushing it using a 24‑G needle can assess its patency.
High negative suctioning can block the intrathecal part of the
catheter and must be avoided.
Surgical technique
The surgery was carried out under general anesthesia (GA).
Patients were placed in the left lateral decubitus position
with both the knees flexed and belts were tied for safety.
Painting and draping were done from the lumbar area, right
flank, and up to the umbilical area. A 1‑cm incision was
made in the paraspinal area between L4‑5 or L5‑S1 spinous
process [Figure 1]. A subcutaneous tunnel was made from the
lumbar incision to the flank, and the peritoneal end of the shunt
was passed through it. A 14‑G Tuohy needle was inserted in the
midline with the beveled end pointing cranially. After entering
the subarachnoid space, the stylet was partially withdrawn
to check for its position in the thecal sac; the stylet was then
completely taken out and the lumbar end of the catheter with
guidewire was inserted up to 8–10 cm followed by withdrawal
of guidewire and Tuohy needle. The extra length of the thecal
catheter was cut and connected to the metal connector with the
peritoneal end. The connector was fixed to the lumbar fascia
with the help of a suture collar, and the incision was closed.
The patient was turned to a supine position and repainted
 Sinha, et al.: Lumboperitoneal shunts

and draped up to the periumbilical area. The abdominal
incision was already marked before the draping was opened,
a small subcutaneous tunnel was made from the abdominal
incision to the previous flank incision, and the catheter was
taken out from the abdominal end. The abdominal end was
inserted by the trocar and cannula technique. Postoperatively,
patients were shifted to the ward, IV antibiotics were given
for five days, and most of the patients were discharged by the
7th postoperative day.
Results
In total, 426 patients underwent LP shunt during the study
period with a 1‑year follow‑up. Age ranged from 16 to
72 years with a mean of 40.4 ± 12.2 years. There were 255 male
and 171 female patients. The most common indication was
tubercular meningitis (TBM) with hydrocephalus (293 patients,
68.8%) followed by IIH. Table 1 shows the indications for LP
shunt, percentage of neurologically improved patients, and
complications. LP shunt was effective in relieving the raised
ICP in 90% of CSF rhinorrhea patients after the repair. Overall,
301 patients (70.6%) had neurological improvement during
follow‑up. GCS improved in 68.9% of patients in TBM. GOS was
5 in 51.2% (n = 150) and 4 in 3.4% (n = 10) at 1‑year follow‑up.
No patient needed laminotomy or abandoning the procedure.
Shunt‑related complications occurred in 112 (26.29%) patients,
the commonest of which was shunt obstruction, which occurred
in 37 patients (8.6%) [Table 2]. Seventeen (3.9%) patients had
shunt infection, and four (0.9%) patients had extrusion of
the abdominal end of the shunt. The shunt was exteriorized
in a sterile bag, and reinsertion was done after obtaining a
normal CSF profile. Transient postural headache was seen
in 46 (10.7%) patients, which gradually improved. During
follow‑up, 26 patients of TBM died within 2–3 months. These
patients had poor pre‑procedure GCS scores. No patient had
procedure‑related mortality. As probably hydrocephalus or
shunt complication was not the cause of their death, they were
not counted as complications in the present study.
Discussion
A ventriculoperitoneal shunt can be performed in most cases of
communicating and obstructive hydrocephalus. Being a cranial
procedure, it carries its own set of possible complications. The
LP shunt is an established but infrequently used procedure. If
used with strict selection criteria and meticulous technique, the
procedure has optimal results for all cases of communicating
hydrocephalus.[11,17,18] The biggest advantage of LP shunt is
it being extracranial and the ability to be performed in even
small‑sized ventricles. Although in this article we did not
perform any direct comparison between VP and LP shunt, Aoki
found that the incidence of infection and malfunction with an
LP shunt was significantly lower than VP shunt after comparing
207 and 120 cases of LP and VP shunts, respectively.[1] Owing
to lack of brain penetration and shorter hospital stay, an LP
shunt is often preferred by the patients and relatives.[19] There is
also an ongoing randomized controlled trial to address which
procedure is more effective and safe.[20]
In our study, neurological improvement was seen in 68.9%
for TBM, 80.8% for IIH, and 45.4% for NPH. Results in TBM
depend upon preoperative neurological status, raised ICP,
preoperative CSF protein content, and basal infarcts; thus, their
workup with appropriate investigations is critical. Preoperative
provocative testing with large volume lumbar CSF drainage
or extended lumbar drainage in NPH has shown positive
results in up to 91%.[5,21–24] In our study, all 10 out of 22 (45.4%)
patients of NPH with gait disturbance as the primary symptom
recovered significantly, whereas the rest had no significant
improvement. Early surgery before an established visual field
defect improves outcomes in IIH.[17,25] LP shunt leads to a global
reduction in intracranial pressure and improves headache and
papilledema.[26] LP shunt can also effectively treat visual field
defects due to herniation of optic apparatus in empty sella
syndrome.[27] Obstructive hydrocephalus is a contraindication
for LP shunt; in such cases, VP shunt or endoscopic third
ventriculostomy is ideal.
Common complications of LP shunt are shunt block, shunt
infection, CSF leak, shunt breakage, or over‑drainage
complications such as acquired Chiari, subdural hematoma
or hygroma,[1,2,4,26,28] and failed needle insertion.[4,26] [Table 3]
Shunt block is the most commonly encountered complication,
ranging from 4% to 14%.[1,11,29] There were 37 (8.6%) shunt
blocks in our study. These patients underwent shunt revision

Table 1: Indications for LP shunt, number of patients, neurological improvement, and complications
Diagnosis Indication and selection criteria Number of Neurological Complications
patients improvement (%) (%)*
TBM with Hydrocephalus Communicating hydrocephalus 293 202 (68.9) 43 (14.6)
Normal protein content in CSF
IIH Failed Medical treatment 47 38 (80.8) 07 (14.8)
Progressive visual field defect with decreased vision
NPH Gait or memory improvement with high volume CSF 22 10 (45.4) 04 (18.1)
drainage (>30 ml)
Spontaneous CSF Rhinorrhea Raised ICP and persistent leak after surgical repair 10 09 (90) 01 (10)
Miscellaneous: Decrease in size of pseudomeningocele with 54 42 (77.7) 06 (11.1)
Post traumatic hydrocephalus‑ 27 repeated lumbar taps
Post‑craniotomy/spinal surgery Not responding to conservative trial
Pseudomeningocoele or CSF leak‑ 23
slit ventricle‑ 04
Total 426 301 (70.6) 61 (14.3)
*Excluding temporary postural headache

Neurology India | Volume 69 | Supplement 2 | November-December 2021 S483

 Sinha, et al.: Lumboperitoneal shunts
Table 2: Complications of LP shunt in the present
study
Complications No. of patients (%)
Failed needle insertion Nil
Shunt breakage and CSF leak 08 (1.8)
Shunt block 37 (8.6)
Shunt infection 08 (1.8)
Shunt extrusion 08 (1.8)
Over drainage symptoms
Temporary postural headache 46 (10.7)
Subdural hygroma Nil
Subdural hematoma Nil
Acquired ACM Nil
Total 107 (25.1)
and improved symptomatically, except for one patient of NPH.
Appropriate length (7-10 cm) prevents both over drainage and
under drainage complications. The thecal end of the LP shunt
should be fixed to the lumbar fascia to avoid its migration.
Preventing kinking of the catheter is of utmost importance to
prevent its blockage. We suspect the shunt blocks if there is a
reappearance of symptoms and signs and dilation of ventricles.
In doubtful cases, we inject iohexol contrast in the lumbar region
below the shunt tube and take CT scans after 30–60 minutes. The
contrast flows in the shunt tube and abdomen in case of patency.
Radionuclide CSF shuntography is another method to determine
the shunt patency. It entails the injection of 99mTc‑DTPA via
lumbar puncture and taking serial imaging of skull and abdomen
at 1, 3, 6, and 24 hours.[30] Laparoscopy can also be helpful for
the diagnosis and management of shunt block.[31]
Shunt infections have been reported in 1%–9% of LP
shunts.[1,2,4,8,11,29] We had 17 (3.9%) shunt infections. Position
change for abdominal‑end insertion with chances of sterility
breach is a possible cause of infection.[2] It can be avoided
by proper care of the catheter while changing the position.
We secure the catheter in a mop and repaint the abdomen
after changing the position to supine. A transportation board
to facilitate changing patient position without changing
the surgical drapes can also be used.[32] Few authors have
also inserted the peritoneal end in lateral position with
laparoscopic‑assisted technique.[33–37] Endoscopic‑assisted
retroperitoneal placement of the abdominal end is also possible
for patients with previous abdominal surgeries or peritoneal
adhesions.[38] Some centers practice the two‑surgeon technique
by simultaneous insertion of lumbar and peritoneal ends in the
left lateral position to reduce time and infections. It is also an
excellent technique. Antibiotics, exteriorizing the shunt, and
revision can control the infections. Emergency scheduling and
prolonged duration of surgery have also been suggested as the
causes of infection.[26]
Shunt extrusion occurred in four (0.9%) patients. Extruded
shunts were removed, and a new assembly was inserted.
Anchoring the thecal end to the lumbar fascia is vital. Raised
abdominal pressure and a strong force produced by lumbar
movements are related to migration and extrusion of shunts.[39,40]
Failed needle insertion has been reported in a few series.[26]
Patients with severe kyphoscoliotic deformity, severe LCS,
S484 Neurology India | Volume 69 | Supplement 2 | November-December 2021
and calcified ligamentum flavum should not be selected for
LP shunt procedure.[2,4] Adequate lumbar flexion, which is
possible under general anesthesia, reduces failed attempts.
In difficult cases, C‑arm fluoroscopy can help to visualize the
interspinous interval.
LP shunt over‑drainage may manifest as acute subdural
hematoma or hygroma. Rarely, it can manifest as tension
pneumocephalus,[41] subarachnoid hemorrhage, intracerebral
hematoma, or development of acquired Chiari malformation
and syringomyelia.[42,43] Intracranial hypotension occurs due
to siphoning effect in an upright position.[44] Patient might
present with symptoms of headache, nausea, or vomiting in
an upright position and symptoms get relieved on lying down.
One can manage pressure regulation by the length of the
lumbar catheter. More the length of the lumbar catheter, more
will be the resistance to CSF flow. The lumbar end is also of
small diameter, which helps in increasing the resistance to CSF
flow and decreases the chances of over‑drainage. Incidence of
ACM was reported high in a few initial series and even stated
as a rule;[42,43] however, it was very low in recent ones.[1,11,45]
Moreover, >95% of these patients have only radiological
abnormality and are clinically asymptomatic.[43] The actual
incidence of radiological ACM but clinically asymptomatic
may be higher in our series (as we did not perform routine
MRI); however, the clinically symptomatic ones were not
observed. A short thecal end could result in over‑drainage
and using 7–10 cm decreases this complication.[2] ACM was
not found with the usage of valves.[46] Altering the construct
of the LP shunt by inserting a programmable valve can
lead to the clinical and radiological reversal of the tonsillar
herniation as well as a reduction in an associated syrinx. It
could also help in varying the drainage rates according to
the clinical condition.[47,48] In a case of secondary ACM due
to LP shunt, a chance should be taken for altering LP shunt
dynamics prior to attempting a VP shunt or decompressing
the posterior fossa.[45] Flushing the valve and adjusting it
might be easier if it is fixed with the paravertebral spinal
muscles.[49] In our study, over‑drainage symptoms occurred
in 46 (10.7%) patients, which improved over 3–7 days with
postural adjustment. No serious and permanent over‑drainage
complications were seen.
Other minor complications can be back pain with or
without sciatica, hamstring tightness, foot deformities,
lumbar hyper‑lordosis, and kyphoscoliosis. Most of these
complications were reported with old shunt systems made of
silastic material.[2]
The limitation of our study is its retrospective nature. There
was no comparison between LP and VP shunt. Future studies
may perform a randomized controlled trial between LP and
VP shunts for communicating hydrocephalus.[20]
Conclusion
LP shunt is a safe and effective technique for the treatment of
communicating hydrocephalus due to refractory idiopathic IIH,
post‑TBM hydrocephalus, NPH, and refractory postoperative
CSF leaks. It can be used as an effective alternative to
ventriculoperitoneal shunts in patients with post‑TBM
hydrocephalus. The optimal benefit of this procedure can
 Sinha, et al.: Lumboperitoneal shunts

Table 3: Complications, their causes, and their avoidance

Complication Predisposition/causes Avoidance
Failed needle insertion Thick obese patients Adequate head and knee flexion to open up the
Spinous process not palpable interspinous area
Severe lumbar canal stenosis or calcified ligamentum C‑Arm may be utilized for localization of spinous process
flavum or kyphoscoliotic deformity and interspinous area
Pre‑operative anticipation X‑ray Lumbosacral spine
Shunt fracture Thin, malnourished patients with less subcutaneous Slightly paraspinal incision can be taken to prevent
fat extrusion of the connector
Connector not properly fixed The connector should be fixed to underlying fascia
Vigorous lumbosacral movement in children Suture collars should be applied at lumbar end
Connecting with intrathecal end may tear the Proper care should be taken while connecting metal
intrathecal catheter connector with a thin intrathecal catheter which is likely to
tear
Guidewire can be used to cannulate lumbar end.
Shunt block Long peritoneal catheter 7‑10 cm of intrathecal catheter and shortening of the
Kinking of the catheter at connector site peritoneal catheter to be avoided
Improper fixation of the catheter Shunt with anchoring sling device or fixation to be done on
Kinking of abdominal end the metal connector, not on the catheter, which may kink
Fixation sutures taken on the lumbar or peritoneal Proper technique should be followed while inserting
catheter which may kink and cause obstruction peritoneal end via trocar and canula
Shunt infection Breach in aseptic precautions during turning. Strict aseptic precautions during positioning and turning
Lower end of the catheter may be contaminated while Use of trocar for peritoneal end insertion
turning.
Long duration of surgery
Surgery during emergency hours
Large rectus sheath incision, improper repair of
rectus sheath in obese patients make cause shunt
extrusion at abdominal end
High intraabdominal pressure in obese patients of IIH
Contamination of surgical site by thigh skin during
lateral painting and draping
CSF leak Shunt fracture most commonly at connector site Due care should be taken while connecting metal
Shunt block connector with an intrathecal catheter to avoid catheter
Shunt extrusion at the abdominal end due to raised tear
intraabdominal pressure in obese patients Proper closure of rectus sheath
Over‑drainage complications: Short intrathecal catheter 7‑10 cm of intrathecal end and proportionate length of the
Subdural hygroma Valveless shunt peritoneal catheter to be used
Acute SDH Sudden raising of the head Use of valve (Medium pressure or high pressure)
Secondary Chiari Use of programmable shunt or shunts with adjustable
malformation valve or shunt with a horizontal vertical slit valve
Low‑pressure headache Gradual raising of head‑end in these patients
Use of valves in non‑resolution of symptoms

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Neurology India | Volume 69 | Supplement 2 | November-December 2021 S487

 Review Article

Access this article online

Quick Response Code:
The Leftover
Shunts ‑ Ventriculosubgaleal, and
Ventriculocholecystal Shunts
Sandip Chatterjee
Website:
www.neurologyindia.com

DOI: Abstract:
10.4103/0028-3886.332246
The two shunts that are performed much less and are included here for completeness are the ventriculosubgaleal
shunt and the ventriculocholecystal shunt. The ventriculosubgaleal shunt is an established treatment of
hydrocephalus following germinal matrix hemorrhage in low‑birth‑weight neonates. It is also used in the
treatment of post‑infective hydrocephalus in children. In our institution protocol, we have used this shunt in a
wide variety of indications, especially in children below six months of age. Ventriculocholecystal shunts are
very much a salvage shunts when all else fails.
Key Words:
ventriculocholectsral shunt, ventriculosubgaleal shunt

Key Message:
In event of failure of all conventional modalities of CSF diversion. The gall bladder and the subgaleal pouch
may be resorted to.

VENTRICULOSUBGALEAL SHUNTS into the ventricular access device (VAD).

V entriculosubgaleal (VSG) shunt is a
simple surgical procedure that offers a
connection between the dilated ventricle and
the subgaleal pouch developed in the opposite
side of the scalp through a small silicone tube.
It is presumed that in a recumbent child, raised
intracranial pressure forces CSF flow from the
ventricle to the tube and then to the avascular
pocket, from where it is absorbed back through
the walls of the pouch kept distended by the
incoming CSF. It is most commonly used
in treating neonates with germinal matrix
hemorrhage as these children have CSF
with high RBC and protein content and also
very low body weight, and are considered
unsuitable for ventriculoperitoneal (VP) shunt.
In our institution, we have used this method
of CSF diversion extensively in post‑infective
hydrocephalus, be it bacterial or tubercular.
Park Neuroscience
This also avoids the complications associated
Service, Park Clinic,
with external ventricular drain (EVD) or
Kolkata, West Bengal,
that associated with repeated transfontanelle
India
ventricular tapping or with insertion of a needle
Address for
correspondence:
Prof. Sandip Chatterjee, This is an open access journal, and articles are distributed under the terms
Park Clinic, 4 Gorky of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0
Terrace, Kolkata, West License, which allows others to remix, tweak, and build upon the work
Bengal, India. non‑commercially, as long as appropriate credit is given and the new
creations are licensed under the identical terms.
E‑mail: sandipchat@gmail.
com For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com
We have expanded the indication of VSG
shunts—such as in posterior fossa tumors,
myelomeningoceles immediately before repair,
in shunt infections, or acute shunt blockage. We
have successively treated older children with
hydrocephalus with VSG shunts routinely up to
3 months of age and also in some children up to
9 months presenting acutely (avoiding an EVD
in those cases).
Our study
We performed a retrospective study involving
the data of 215 patients under the age of
3 months who presented with hydrocephalus
in the period between 2009 and 2018. All the
patients were screened for hydrocephalus
clinically with serial head circumference
measurement, looking for tense and bulged
anterior fontanelle along with subtle signs such
as upgaze restrictions or sixth cranial nerve
paresis. Head circumference measurements
were used as clinical marker for the progression
of hydrocephalus. All the patients underwent
USG scans at the time of presentation and
ventriculomegaly more than 97 th percentile
How to cite this article: Chatterjee S. The Leftover
Shunts - Ventriculosubgaleal, and Ventriculocholecystal
Shunts. Neurol India 2021;69:S488-94.
Submitted: 26‑Sep‑2021 Accepted: 18-Oct-2021
Published: 11-Dec-2021

S488 © 2021 Neurology India, Neurological Society of India | Published by Wolters Kluwer - Medknow
 Chatterjee: Leftover shunts

for age was accepted. MRI scans were done in all except
premature neonates in NICU to detail the anatomy, type of
hydrocephalus, and identification of loculations if present.
Routine analysis of ventricular CSF was done in all the cases
through fontanelle tap to look for cell type, cell count, protein
and sugar levels, and Gram stain and culture.
Our technique for VSG shunt placement is to make a curvilinear
incision in the precoronal region, in line with the ipsilateral
pupil. The dura is cauterized and opened in the lateral angle
of the anterior fontanelle, which is normally open in the
majority of the infants at the age we performed the shunts.
A ventricular catheter is used to tap the ventricle, which is
then attached to a low‑pressure slit spring valve connected
to a small segment of tubing with slits made on either side.
A large subgaleal pocket is created on the opposite side of the
scalp with a blunt dissector being run 270° in exactly the same
plane from the coronal suture to the lamboid suture and then
across the posterior fontanelle extending to the other side in
the back. The temporalis fascia and the forehead are avoided.
The short distal tube is placed in this pouch after checking CSF
flow with the valve tunneled under the skin. The shunt is fixed
by a tacking suture proximally, but the distal flange is kept
dangling [Figure 1]. Compression bandage of scalp is avoided
to allow distension. Our rationale in using a low‑pressure valve
instead of a simple tubing has been that this ensures that there
is no rapid drainage of the CSF causing a large accumulation of
CSF in the subgaleal pouch. In our initial experience of using
plain tubings, often the initial collection of CSF was so large
that there was leakage through the skin or need for multiple
aspirations, neither of which happens when a low‑pressure
valve is incorporated into the system. Moreover, the valve
helps provide a chamber from which CSF may be aspirated
in the future.
CT scans or MRI scans were done routinely after 3 months
of insertion of VSG shunt or earlier if there are any signs of
blockage or malfunction. A  final decision of conversion to
VP shunt is taken at this juncture. In cases where there is
significant CSF collection in the subgaleal pouch, the VSG shunt
is persisted with while it continues to function.
Results
Our series had 35 patients of post‑hemorrhagic hydrocephalus
(PHH) in prematurity presenting at the mean age of 36.5 weeks,
out of which 32 underwent primary VSG shunts. Three patients
had VP shunt done earlier and presented with a failed shunt;
they underwent VP shunt removal and secondary VSG shunts.
Eight of them had concomitant CSF infection.
Among the 82 patients of post‑pyogenic hydrocephalus (PPH),
30 patients presented at the mean age of 1.3 months (early group)
and 52 presented at a mean age of 3.2 months (delayed group);
13 patients had already VP shunts inserted outside [Figure 2].
Further, 41 patients of post‑tubercular meningitis (PTBMH)
hydrocephalus presented at the mean age of 5.6 months, out
of which nine patients were in grade 4.
Thirty‑eight patients presented with post‑meningomyelocele
(PMMCH) hydrocephalus, of which six had failed VP shunt.
Complications associated with VSG shunts were CSF leak (10%),
blockage (15%), infection (7%), and migration (2%). The mean
duration of VSG shunts were 63 days in PMMCH, 60.1 days
in PPH, 52 days in PTBMH, and 40.6 days in the PHH group.
VSG revisions were maximum in the PTBMH group (54%),
followed by the PPH group (21%), PHH cohort (13%), and the
least in the PMMCH group (12%) [Figure 3].
We think that our success lies in the primary outcome of
VP shunt conversion rate—39% in the PHH group and 23%
in PMMCH group were ultimately shunt‑free. However,
permanent CSF diversions were required in 90.2% of PTBMH
and 97% in the PPH group.
Besides these, in a significant number of PPH patients with
multiloculated hydrocephalus, we had used VSG shunts after
multiple endoscopic fenestration procedures to reduce the
number of loculations before putting in final VP shunts.

While removing the VSG shunt, a suture of 1/0 silk is used TOTAL NUMBER OF CASES
percutaneously to tie up the distal catheter (a procedure done
100
under sedation). If there is no clinical or radiological evidence
80
of ventriculomegaly after 72 hours, the VSG shunt is removed
under general anesthesia. 60
40
20
0
PPH PTBMH PHH PMMCH POST
FOSSA
TUMOUR
PREVIOUS SHUNTS

15 13

10
3 3 4
5
0
PPH PTBMH PHH PMMCH

Figure 1: Our technique for VSG shunt Figure 2: Indications for VSG shunts

Neurology India | Volume 69 | Supplement 2 | November-December 2021 S489

 Chatterjee: Leftover shunts
2%
CSF LEAK
10%
7%
BLOCKAGE
INFECTION
MIGRATION
15%
Figure 3:Complications of VSG shunts
We had used this VSG shunt in 11 cases of infantile
hydrocephalus associated with posterior fossa brain tumors
where the infants had significantly raised intracranial pressure
at presentation and were not considered fit for definitive
surgery. Here the procedure was performed as an emergency.
VSG shunt was done prior to the posterior fossa surgery to
allow slow decompression. EVD was avoided in all cases.
Conversion to VP shunt was 50% in these cases.
Four children with acute hydrocephalus with precipitous shunt
blockage underwent VSG in lieu of EVD to be converted to
formal shunts within a month.
Lastly, three infants having hydrocephalus following
traumatic brain injuries and associated with severe
comorbidities (pneumothorax, hemoperitoneum, and long
bone fractures) underwent VSG shunts as interim measures to
avoid longer surgical and anesthetic procedures of VP shunt.
Discussions
VSG shunt was first described in 1896 by von Mickulicz,
followed by successive publications from Schramm (1899),
Senn (1903), Horseley (1906), and Krause (1908). Renewed
interest came in 1977 when Perret and Graf presented a series
of 173  patients suffering from tumors and subdural fluid
collections.[1]
There are many options in treating a neonate with
hydrocephalus. In those with open fontanelle, ventricular tap
on a repeated basis can be a temporizing measure, especially in
CSF laden with RBC or infection. However, the disadvantages
are that they are labor‑intensive, require strict aseptic protocol
and environment, and repeated taps may lead to frontal lobe
gliosis with resultant development of a seizure focus.
Lumbar puncture is an option in communicating
hydrocephalus, but one must remember that CSF spaces are
non‑communicating (either at foraminal or at arachnoidal
level) in a majority of our cohort and repeated lumbar taps
may lead to focal arachnoiditis with subsequent tethering of
the spinal cord. In fact, the published guideline[2] has a level 1
non‑recommendation for use of serial lumbar puncture.
S490 Neurology India | Volume 69 | Supplement 2 | November-December 2021
External ventricular drainage is the most direct method of
quick relief of raised intracranial pressure, but it carries a high
rate of infection even in the best of the setups. Furthermore, it
is difficult to maintain in a non‑neurosurgical setup like in a
general neonatal intensive care unit (NICU) and runs the risk
of disconnection, blockage or over drainage, if not maintained
correctly. Protein and electrolyte loss through EVD also require
meticulous monitoring in a sick child.
VP shunt is a rational option, but its use is limited in
small neonates. Infants with less than 2 kg bodyweight do
not tolerate shunts and many premature neonates have
associated immature peritoneum and possible gut infections
such as necrotizing enterocolitis, negating the possibility
of an abdominal procedure. In post‑infective cases, highly
proteinaceous CSF leads to slow CSF flow, making the shunt
more prone to blockage and infection, and also causes irritation
of the peritoneum leading to ileus. In cases of huge posterior
fossa tumors, shunting for hydrocephalus may lead to upward
herniation through the tentorium. The cost of shunt procedure
and revisions are quite high as compared to temporizing
procedures. Delaying shunt procedures may lead to better
survival and subsequent reduced number of repeat surgeries
and costs. In patients with acutely raised intracranial pressure,
the VSG shunt insertion requires less than 10 minutes of
operating time.
Endoscopic third ventriculostomy (ETV) is not the procedure
of choice in a neonate or in an acute setting. However, its
use is also technically difficult if not impossible in cases of
post‑infectious hydrocephalus due to hazy CSF, multiple
loculations, thick septum, and hypervascularity increasing
the possibility of intraoperative bleeding. In hydrocephalus
due to meningomyeloceles or posterior fossa tumors, though
there are numerous reports of successful ETV procedures, in
our practice, we have found the space in front of the basilar
artery is very small in these cases. ETV is fraught with failures
in small children with these problems.
VAD is a useful temporary measure wherein a small reservoir
is placed subcutaneously connected to the ventricle. This
will require frequent tapping as the reservoir fills in no time.
Each tap carries a risk of introducing iatrogenic infection. In
small neonates with thin skin, especially in a malnourished
population like ours, the reservoir tends to extrude through
the skin causing CSF leak and great difficulty in subsequent
management.
VSG shunts offer the best of both worlds. It is a closed device,
thus negating the infection rate and fluid loss risk of an EVD.
It is a short surgical procedure (can be done at the bedside),
giving an advantage in acute settings. It avoids the abdominal
complications of the shunt and the risk of ETV in small
infants. As compared to VAD, the shunt assembly is flatter
and the receptive cavity (subgaleal pocket) is large; thus,
chances of blockage, extrusion, and CSF leakage are much
lower. Compared with VAD, VSG shunt group had fewer
taps (1.6 vs. 10 taps) and longer time interval before placing
VP shunt (80.8 days vs. 48.8 days).[3] Fountain et al.[4] in their
meta‑analysis of 338 publications comparing the use of VAD
and VSG found out that a significant proportion of patients
with a VSG require less tapping. The pooled outcome of nine
 Chatterjee: Leftover shunts

studies with VSG shunts for posthemorrhagic hydrocephalus
described 9.6% as rate of obstruction, 9.2% rate of infection,
but mentioned that there was the arrest of hydrocephalus in
13.9%, 12.2% requiring revision, and 58.7% leading to good
neurodevelopmental outcome.[5]
The golden advantage of VSG shunt is its longevity. The
average duration of these shunts in our setting was 53.9 days,
that is, almost 2 months. Eid et al.[6] in their review of 185 VSG
shunts found an average longevity of 37.4 days in the primary
group and 32.4 days in the secondary group. The majority of
the shunt dysfunctions were due to pocket problems and not
due to catheter blocks. In the series of Fulmer et al.,[7] it was
also observed that most of the failures were due to failed
subgaleal CSF absorption (pouch too full or too empty) and not
because of the catheter blockade. Tubbs et al.[8] showed other
complications of VSG shunts to be infection (5.9% vs. 7% in
our group—probably due to much varied cohort of patients),
bleed (1.1% vs. none in our group) and leak (4.7% vs. 10% in
our group due to increased prevalence of malnourishment in
our study group). It may be pointed out that despite using a
valved shunt instead of a valveless tubing as in other studies,
our rates of shunt blockage were low.
In neonatal post‑hemorrhagic hydrocephalus of prematurity,
VSG offers a significant advantage over other methods of
CSF diversion such as EVD and VADs. Not only the internal
diversion procedure is better from the risk of infection but also
the small surgery puts very little stress on the premature child.
There have been reports of subgaleal shunt being performed
under local anesthesia and sedation without intubation.[9]
Interestingly, in one series, the mean life span of VSG shunts
placed at NICU was much longer than that placed at OR (73 vs.
43 days).[10] Our series showed that 40% of the children in this
subgroup required no further shunts, a much higher incidence
as compared to other series.[11] In some centers using VAD as
an alone temporizing measure, the VP shunt conversion rate
was as high as 95%.[12]
In the post‑pyogenic group, our policy of routinely analyzing
all CSF before deciding for shunts has been successful in
isolating a fair number of asymptomatic patients with CSF
infection[13] possibly due to partially treated meningitis, a very
common finding in our population. VSG shunts offer a fantastic
temporizing tool allowing the CSF to recover, with a mean VP
shunt conversion time of 60.1 days, though literature shows
a much higher stay up to 75.6 days in the Nagi series.[14] The
conversion to VP shunt has been the highest in this group due
to persistence of multiloculation, thick ventricular walls, and
failure of resorption at the level of arachnoid villi. However, in
only 1 case, the subgaleal pouch got infected in this group; this
necessitated a change of the VSG shunt to the opposite side.
meningomyeloceles or brain tumors, VSG shunt can help the
children to tide over the crisis period and a significant number
of them can be made shunt‑free. In our institution, in these
cases, we ligate the VSG shunt percutaneously with a heavy
suture and follow the child clinically and radiologically for 72
hours. If there is no ventricular dilation, we remove the VSG;
otherwise, convert them to VP shunts.
Ventriculocholecystal shunts
Introduction
Ventriculoperitoneal shunt (VP) is the most common surgical
procedure in hydrocephalic children. However, occasionally,
some unfortunate children have to undergo multiple shunt
revisions with subsequent sequalae of abdominal scarring,
adhesions, pseudocysts, and chronic infections, which
renders the peritoneum unfit for absorption. In these patients,
ventriculocholecystal shunts (VC) provides a viable, easy, low
risk, and economical option of CSF diversion as compared
to traditional options such as ventriculopleural (VPL)
or ventriculoatrial (VA) shunts [Figure 4]. We report
our experience of three cases with ventriulocholecystal
shunts [Figure 5].
Case 1
A 5‑year‑old child with post‑tubercular meningitic
multiloculated hydrocephalus presented in 2019 with
abdominal pain, distension, and fever. He had undergone
multiple CSF diversionary procedures since childhood,
namely ventriculosubgaleal shunt, endoscopic fenestrations,
and then ventriculoperitoneal shunt, which was revised once
2 years before this presentation. This time, pus was seen to
be coming out through the abdominal wound; there was
local tenderness and guarding but no peritonitis or systemic
sepsis. The pus and shunt CSF was sent for bacteriological
analysis. The acute abdomen was managed conservatively
in consultation with a pediatric surgeon. The pus culture
showed growth of E. coli, CSF was sterile, and head CT showed
ventriculomegaly with periventricular lucency. Abdominal
X‑ray was non‑confirmatory, and ultrasound examination of
the abdomen showed localized dilated loops of the small bowel.
Sensitive antibiotics were started, but due to non‑resolution

With a single revision, life can be extended even further. Repeat

VSG was required in 21% of post‑pyogenic hydrocephalus
patients comparable to 23.8% of the patients in another Indian
series.[15] However, revision rates are high in post tubercular
meningitis probably because of very proteinaceous CSF
content.

In patients with temporary hydrocephalus, such as post Figure 4: Technique of insertion of the peritoneal end of the catheter into the gall
hemorrhagic, post‑traumatic, and those associated with bladder

Neurology India | Volume 69 | Supplement 2 | November-December 2021 S491

 Chatterjee: Leftover shunts
Figure 5: Cases who underwent ventriculocholecystal shunt
of the acute abdomen, it was decided to surgically explore
the abdomen. At surgery, it was found that the distal end of
the shunt had perforated the intestinal wall partly leading to
intense local inflammation. Pockets of peritoneal adhesions
were also seen on the opposite side during this laparotomy,
presumably due to multiple surgeries or due to old tubercular
scarring. The shunt was separated, intestinal partial perforation
repaired, and the shunt was exteriorized. It was draining
adequately. As the child was shunt‑dependent, the choice after
few days was to re‑implant the shunt either in the pleura (risk
anticipated was adhesions from previous tuberculosis) or in
the atria (risky due to chances of systemic sepsis, endocarditis,
and cardiac overload, any of which this frail child would hardly
tolerate). Thus, it was decided to implant a fresh shunt in the
gallbladder after the size and drainage was checked with
abdominal ultrasound At surgery, the ventricle was tapped
through a new burrhole and a fresh medium pressure slit valve
shunt was tunneled to the abdomen. A subcostal incision was
given, the gallbladder was dissected by the pediatric surgeon,
and a small fenestration was done at the fundus through
which the 2 cm of a distal end of the shunt was inserted.
A purse‑string suture ensured good snug fitting of the shunt
and the wound was closed in standard fashion. The child was
given antibiotics for 7 days and a repeat ultrasound showed
perfect shunt end position and a contractile gallbladder.
At 8 months of follow‑up, the child is asymptomatic. Two
more repeat ultrasound scans of the abdomen and a CT head
showed a contractile gall bladder containing the shunt with
decompressed ventricles.
Case 2
This was a 3‑year‑old girl with post‑bacterial meningitis
producing hydrocephalus who first underwent endoscopic
S492 Neurology India | Volume 69 | Supplement 2 | November-December 2021
breaking down of loculi (the hydrocephalus being multiseptated)
and then a ventriculoperitoneal shunt, which was revised twice
in the same year due to lower end blockage. One year later, she
developed abdominal pseudocyst, for which exteriorization
of the shunt was necessary. On reinsertion into a different
quadrant of the abdomen, she developed intestinal obstruction.
The shunt was completely removed, a fresh external ventricular
drain was inserted, and the intestinal obstruction was treated
conservatively. However, as there was no resolution of the
obstruction, laparotomy was needed and multiple adhesions
were lysed. A ventriculopleural shunt was done. Within
4 weeks, she developed respiratory distress and developed a
pleural effusion that needed to be drained. It was then decided
to attempt a ventriculocholecystal shunt. This was done in
the same manner as described for the previous case after the
ultrasound abdomen revealed a normal gall bladder and biliary
system. Repeated ultrasound examinations were done every
month for the next four years, and she remains asymptomatic
today, 9 years after the surgical procedure.
Case 3
A 2‑year‑old male child with a ventriculoperitoneal shunt
done elsewhere presented with ventriculitis and peritonitis
following overwhelming sepsis. He also has tubercular
cavitation in his left lung apex, and had hydronephrosis
for which he had undergone surgery 3 months previously.
The child was treated with a ventriculosubgaleal shunt, and
after the ventriculitis resolved, he underwent an endoscopic
third ventriculostomy, which failed and he required a
ventriculoperitoneal shunt. Unfortunately, he re‑presented
after 6 months with extrusion of the shunt through the anus,
and the shunt was exteriorized. There was no peritonitis, and
after 10 days, a new ventriculoperitoneal shunt was inserted.
Unfortunately, he developed intestinal obstruction again,
and this time after the obstruction resolved with conservative
treatment, it was decided to do a ventriculosubgaleal shunt
as the gall bladder and biliary system appeared to be normal
on screening ultrasound. The procedure was performed in the
usual manner, and he went home uneventfully. The ultrasound
examination after 6 months showed a good position of the
shunt with a slightly dilated gallbladder, and apart from his
general cachexia the child was well with the decompressed
ventricular system on CT scan. Four months later, he presented
with severe abdominal pain and vomiting and there was a
distended gallbladder on ultrasound examination, and he had
features of cholecystitis. As conservative treatment failed, he
underwent a cholecystectomy, and the entire shunt system had
to be removed and replaced with a ventriculosubgaleal shunt.
The child was subsequently lost to follow‑up 6 months after
this procedure when the parents refused further shunt surgery
as the VSG shunt was still functional at that time.
Discussions
VC shunt was first described in 1995 by Smith et al.[16] as a
new treatment of hydrocephalus. Infection and blockage are
the two cardinal causes of revision of a VP shunt. In children
who are shunt‑dependent or in cases of multiloculated
hydrocephalus, multiple shunt revisions may lead to scarring
of the abdominal wall, visceral adhesions, and intra‑abdominal
compartmentalization. Any new shunt in them will be doomed
to dismal failure. The common and practical options in these
 Chatterjee: Leftover shunts
cases are to do endoscopic third ventriculostomy (ETV),
VA shunt, or VPL shunt. Anecdotal reports are there in
the literature for shunts connecting the ventricle with the
pericardium, inferior vena cava, saphenous veins bladder,
ureter, stomach, and fallopian tubes.[17‑19]
ETV is difficult and less successful in most cases of multiloculated
hydrocephalus and congenital communicating hydrocephalus,
particularly in low‑weight children with poor peritoneal
absorption. VA shunt is an established procedure but technically
challenging. It also carries a risk of bacterial endocarditis, systemic
sepsis, and fluid overload, which may be life‑threatening in these
children. VPL shunt is easy, but the pleural space is neither as
accommodative nor as resorptive as the peritoneum, and as in
case 2, may give rise to serious complications.
VC shunt is physiological as the gallbladder is an excellent
absorptive organ, reabsorbing water and electrolytes from the
bile at the rate of 1500 cc daily, thus concentrating the bile.[20]
Further reabsorption also occurs in the intestine distally. The
mean pressure in a conventional shunt (8–12 cm H2O) is almost
equal to portal venous pressure (8–14 cm H2O), facilitating
controlled drainage. There has been a suggestion that the
VC shunts work less if preoperative EVD output exceeds
30 ml/h.[21] Contraction of the gallbladder also creates a drive
for the CSF to be mobile at all times. Thus, VC shunt is an
useful alternative unless there is cholecystitis, gall bladder
sludge, and bile‑duct stenosis. For this reason, preoperative
ultrasound study of the gallbladder and bile duct is a must.
Relative contraindications are hemolytic diseases such as
sickle cell anemia in which gall bladder calculi are common.
Another contraindication is Salmonella infection, which has
a predilection for bile involvement. Prophylactic antibiotic,
therefore, is a must in endemic zones like ours. In a previous
series, the infection rate was 25% in the early months and
37.5% in late months.[22] The common organisms are E. coli
and Klebsiella, but most series refer to Staph epidermis as
the commonest agent.[23] There has been a single report of
symptomatic cholelithiasis after VGB shunt[9] and a death due
to biliary ventriculitis.[24]
In a more recent review of a series of VC shunts, Bernstein
et al.[25] observed a long‑term success rate of 62.7% and an
infection rate and obstruction rate of 10.2% each, akin to a VP
shunt. Other series also echo the same picture.[12‑16]
Conclusion
VC shunt is a viable alternative in case of failed VP shunts in
hydrocephalic children with the compromised abdomen and
where ETV is not an option. It is easy to do, less risky than VA
or VPL shunts, and drainage is quite optimal.
NOTE: This chapter is an amalgamation of two articles written
by the senior author which have been published in Childs
Nervous System and Neurology India on the same subject.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S493
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4. Fountain DM, Chari A, Allen D, James G. Comparison of the use
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preterm infants: A systematic review and meta‑analysis of outcomes
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et al. Complications of ventriculosubgaleal shunt in infants and
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long –term outcomes in premature infants with post hemorrhaghic
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11. Rahman S, Teo C, Morris W, Lao D, Boop FA. Ventriculosubgaleal
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hydrocephalus. Childs Nerv Syst 1995;11:650‑4.
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16. Smith GW, Moretz WH, Pritchard WL. Ventriculo‑biliary shunt; a
new treatment for hydrocephalus. Surg Forum 1958;9:701–5.
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18. P h i l i p s   M E , S c h w a r t z   S B , S o u t t e r , S u t t o n   L N .
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S494 Neurology India | Volume 69 | Supplement 2 | November-December 2021

 Original Article

Access this article online

Quick Response Code:
Shunt Complications – Staying Out of
Trouble
Chidambaram Balasubramaniam

Website: Abstract:
www.neurologyindia.com
Background and Objective: To analyze the common problems in shunt surgery and measures to avoid them.
DOI: Management of hydrocephalus takes up as much as 50% of a pediatric ‘ ‘neurosurgeon’s  time, and these are
10.4103/0028-3886.332256 notoriously prone to complications. In this article, the author analysis his series of ventriculoperitoneal shunts
and discusses his technique, nuances and avoidance of shunt complications.
Methods and Materials: The author will review common issues related to hydrocephalus shunt management
with a review of 549 procedures and associated complications.
Results: Key features and basic principles of complication avoidance in shunt surgery is provided. The analysis
looks into the complications and ways to avoid them based on the author’s experience
Conclusions: Specific measures may be adopted to minimize or avoid these complications. These will be
discussed based on the author’s series and experiences.
Key Words:
CSF shunts, shunt  complications, avoiding shunt complications

Key Message:
It must be emphasized that even though the problems and complications experienced are more or less the
same by most surgeons, the techniques used to prevent and manage them and their occurrence will vary from
surgeon to surgeon. Each surgeon must adopt a strategy applicable to the particular situation in question.

“A nd hardly in a single other condition have

cure been more elusive or so often wrecked on
purely mechanical obstacles”: Leo Davidoff.
Treating hydrocephalus by shunt procedures
or endoscopy  ‑  takes up a significant working
time of pediatric neurosurgeons. Managing the
complications that arise from these operations
takes up an equal amount of time for a pediatric
neurosurgeon.
This author will discuss the various complications
and methods to minimize them based on
personal experience. Most have been learned
by the author over the years, and the process
Department continues. Although much time and effort have
of Paediatric been spent on studying these issues, they still
Neurosurgery, remain a commonplace occurrence. It must be
Kanchi Kamakoti Childs emphasized that even though the problems
Trust Hospital, Chennai, and complications experienced are more or
Tamil Nadu, India less the same by most surgeons, a variety of
techniques are used to prevent and manage
Address for
correspondence: them. Each surgeon must adopt a strategy
Dr. Chidambaram applicable to the particular situation in question.
Balasubramaniam,
New 14 Old 26 Second This is an open access journal, and articles are distributed under the terms
Main Road, Cit of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0
Colony, Mylapore, License, which allows others to remix, tweak, and build upon the work
Chennai ‑ 600 004, non‑commercially, as long as appropriate credit is given and the new
creations are licensed under the identical terms.
Tamil Nadu, India.
E‑mail: bchidu@gmail.com For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com
The complications (or problems) are many and
may occur at any time in the patient’s life, i.e.,
the author has seen shunt issues occurring in
adulthood (device inserted in infancy).
Cerebrospinal fluid (CSF) shunts remain among
the most failure‑prone life‑sustaining medical
devices implanted in modern medical practice.
Reported failure rates are 30–40% at one year
and approximately 50% at two years in pediatric
patients[1‑8] with a 10‑year failure rate reaching
70%.[9,10] By the end of the first year, 40% of
children may have shunt‑related problems, and
the numbers rise to 50% at the end of the second
year. It has been estimated that a child who
has undergone a shunt placement in infancy
will experience 1.5 shunt‑related problems by
reaching adulthood. It is not possible to predict
who will develop a shunt problem. In Raimondi’s
analysis, a child with hydrocephalus will average
2.1 revisions per 3  years of life with the range
being no revisions for the first 15 years of life to
21 modifications in the first year of life”.[11] When
compared to the aviation sector flights globally
How to cite this article: Balasubramaniam C. Shunt
Complications – Staying Out of Trouble. Neurol India
2021;69:S495-501.
Submitted: 15‑Jun‑2021 Revised: 01-Oct-2021
Accepted: 19‑Oct‑2021 Published: 11-Dec-2021

© 2021 Neurology India, Neurological Society of India | Published by Wolters Kluwer - Medknow S495
 Balasubramaniam: Shunt complications

between 2002 to 2011, the data translates to 0.6 fatal accidents occur within the first two months of insertion. Skin bacteria,
happened per one million flights, 0.4 per million hours flown, such as CONS  (Coagulase‑Negative staphylococcus) and
and 22.0 fatalities per one million flights or 12.7 per million Staphylococcus aureus, cause most CSF shunt infections[20‑24]
hours flown during this period.[12] with gram‑negative bacteria responsible for approximately
20% of cases.[25]
Much improvement is needed, and since we are dealing with
a biological system, it would be difficult to control the results Simple measures suffice to reduce the infection rate.[26] The basic
despite best efforts. Nevertheless, specific methods which if tenet in reducing shunt infections is to adopt protocols and
implemented, will result in a reduction in the complication rate. strict adherence to them. These protocols are simple to adopt
The methods learned by experience will form the basis of this and implement in daily practice, and these can be discussed
article. We will not elaborate on all the possible complications, and elaborated as follows.[27‑43]
but review the techniques adopted to mitigate them. 1. Shunts have to be done as the first case of the day. It is a
well‑established maxim that surgeries performed late in
Incidence the day have a higher infection rate.
2. Limit of not more than two shunts per day. If several
An analysis of 477 patients (range 32‑week gestation to 17 years) procedures are performed, the infection rate in the
who underwent 1026 surgeries was performed. Of these, there operations performed later is higher. Hence it stands to
were 477 primary shunts and 549 revision surgeries [Table 1]. reason that minimizing the number of shunts completed
in a day is kept to a minimum.
Classification 3. The operation theatre (OT) traffic is kept to a minimum. The
greater the number of personnel in the OT translated into
A simple method of complication classification will be used to a higher infection rate. The number in the OT is governed
review the various issues. on a strictly “need to be their basis”.
4. No one is allowed to enter or leave unless there is an
Four major classifications of complications include: absolute need to do so since the more times, the greater
• Infection the chances of sepsis.
• Functional 5. The skin is prepped, and the prep solution is allowed to
• Mechanical dry on the skin. It is a well‑established fact that if the prep
• Others. solutions are allowed to dry on the skin, the better the
bactericidal effect of the solution.
6. Meticulous clean, sharp dissection is carried out with
Infections
minimal use of cautery. Excessive use of cautery leads
to more significant tissue necrosis resulting in a higher
The incidence of shunt infections varies widely between
infection rate.
various series. The infection rates have been estimated to
7. The shunt system is opened only after the tunnelling is
range from almost 0% to as high as 30%, with more recent
done. Therefore, opening the shunt pack beforehand and
literature showing an incidence between 2 and 5%.[13‑18] The
soakage in antibiotic solution is not needed, nor does it
incidence is decreasing because of an improved understanding
confer any benefit and may lead to contamination of the
of pathophysiology, stricter protocols, and superior hardware.
shunt system.
8. The choice of the antibiotic is governed by the surgeon’s
It has to be emphasized that there is no universal classification
practice and institution protocol. However, a basic
of “shunt infection”. Some experts require positive cultures
antibiotic that covers skin flora is sufficient.
alone, while others accept even the occurrence of fever after
shunt surgery as “ shunt infection “.[19] Most true infections
The child is allowed a shampoo bath on the second post‑op
day and is discharged home.
Table 1: Complications of shunt: personal series
Complications n=549 Antibacterial materials impregnated shunts have shown great
Shunt block 417 promise. Nevertheless, in the author’s opinion, these may not
Haematomas 33 be needed in all cases since simple measures elaborated and
Abdominal 18 discussed above will yield significantly good results.
Ascites/Loculations/Effusion 16
CSF leaks 16 Functional
Mechanical 14
Functional 11 The shunt is placed to divert the CSF from the cranial
Migration 9 compartment to another body cavity to facilitate absorption.
Trapped ventricles 7
In straightforward terms, the shunt performs as a conduit. It is
expected to work at an optimal level constantly, but at times,
Seizures 5
the shunt may “ overdrain “ or “underdrain” and may not drain
Metastases/Pneumothorax/Abscess 1
the CSF appropriately. Either of these may happen, and specific
Pneumothorax 1
measures may help mitigate their occurrence. However, these
Abscess 1 have to be anticipated, and appropriate measures must be
Shunt Infection (Other then abscess) <3% employed.

S496 Neurology India | Volume 69 | Supplement 2 | November-December 2021

 Balasubramaniam: Shunt complications
The functional problems can be subdivided into:
Over Drainage
Overdrainage can be subdivided further into acute and chronic
overdrainage.
Acute Presentations of Overdrainage
Acute over drainage usually occurs when a child with a large
head size uses a low pressure or low‑  very low‑pressure
system. It is also – albeit rarely‑ seen when is a child with a
large head is mobilized too soon after the surgery. These acute
collections usually result from snapping of the draining veins
as the brain “collapses”, the group being often a subdural
hematoma [Figure 1]. This issue can be prevented by mobilizing
a child with a large head slowly. The child is kept supine for
a day or two and mobilized slowly. If the fontanelle is open, it
will serve as a good guide.
Every once in a while, the extracerebral collection may
be sizable and cause a mass effect with features of raised
intracranial pressure. In these instances, the collection and the
shunt have to be addressed together to prevent the worsening
of the clinical condition. The management of these can be
complex. For acute collections, the shunt has to be exteriorized
and kept closed. Then, the hematoma has to be drained through
a needle, a burrhole or a craniotomy as appropriate under the
circumstances. Imaging is repeated after a few days, and the
shunt is revised. In the meantime, if the child develops features
of raised intracranial pressure, the shunt is immediately
opened, and the exteriorized shunt is converted to an external
a
b
Figure 1: (a) Acute SDH from acute overdrainage. (b) Chronic collections resulting
from chronic overdrainage
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S497
ventricular drain. Subsequently, the shunt is revised. If there
are no overt features of raised intracranial pressure, a plain
catgut suture is placed on the distal catheter, and the shunt is
internalized. As the catgut slowly gets absorbed, the CSF will
start draining. When revising the shunt, it may be prudent to
change to a higher pressure system. These manoeuvres will
allow gradual expansion of the brain.
Chronic Presentations of Overdrainage
a. Subdural hygroma
Chronic thin collections are hygromas and do not cause
any mass effect, and the child is asymptomatic and thrives
well. These do not need any treatment apart from watchful
expectancy. However, if a hygroma is persistent and
causing a mass effect, a subdural–peritoneal shunt may be
needed. These shunts can usually be removed after a time.
b. Slit Ventricle Syndrome
Slit Ventricle Syndrome is a problem that is not seen often
but occurs over time after the sutures are fused. In simple
terms, the shunt is over‑functioning,[44] thus leading to
shunt malfunctions. In addition, the ventricles are unable
to expand because of the poor elastance of the brain. These
are the children who are shunt‑dependent. The result is
slit‑like ventricles on imaging with clinical features of shunt
malfunction and raised intracranial pressure. The diagnosis
is one of exclusion since a variety of conditions may
mimic these conditions. The diagnosis can be confirmed
by monitoring the intracranial pressure, although this is
seldom necessary.
a. There are many ways to manage this condition. These
include adding an antisiphon device to the shunt,
revising to a higher pressure system, [45,46] cranial
expansion or morcellation, decompressive craniotomy,
or the addition of a lumboperitoneal shunt. [47]
Performing endoscopic third ventriculostomy is an
option in patients who have obstructive hydrocephalus
and adequate ventricular size.[48,49]
In cases of under drainage, ruling out shunt malfunction due to
obstruction or use of an inappropriate valve (higher pressure
than required) is mandatory.
Mechanical Complications
The most familiar mechanical problem is shunt block. Although
the shunt can get blocked anywhere along its course, proximal
blocks are the commonest site of the blockage[13,50] Precisely, the
obstructions can be intracranial, in the ventricular portion of the
catheter, the valve or the reservoir. These are perhaps the most
typical reason for shunt revisions. The blockage is usually caused
by tissue debris, choroid plexus, or blood. In long‑standing shunt
systems, calcific deposits are seen on the hardware, anywhere
along the catheter [Figure 2]. It should be emphasized that the
incidence of the proximal shunt block is similar irrespective of
ventricular catheter placement – frontal, parietal, or occipital.[50]
Except in very unusual circumstances, the entire ventricular
catheter has to be replaced. “Cleaning or unblocking” the catheter
and replacing it leads to recurrence of the block.
No standard or fixed length of the ventricular catheter can
be recommended in children because of the growing skull.
 Balasubramaniam: Shunt complications

b a b

c
Figure 2: (a) Calcification in reservoir and peritoneal catheter. (b) Choroid plexus
clogging the catheter. (c) Tissue debris in the reservoir

The ideal length of the ventricular catheter is determined by

measuring the distance from the burrhole site to the midline,
and this length plus two centimetres will be the ideal length
of the ventricular to be used [Figure 3]. In addition, distal end
blockages occur, and can be avoided by using an open‑ended
catheter. Since the author started using open‑ended distal
catheters, these blocks have not occurred [Figure 4].
Shunt pullouts, disconnections, and breakage of the catheters
are seen as the child grows. This often occurs in tubes that have
been in place for a long time and have become stiff or have
calcific deposits on them. In these instances, the whole length
of the catheter or even the whole system has to be replaced.
Adding a connector to lengthen the catheter should be avoided.
The incidence of shunt blocks is proportional to the number of
connectors in the system.
Removal of the ventricular catheter can result in bleeding inside
the ventricle or the parenchyma. This is seen if the catheter is
especially if adherent to the choroid plexus or in long‑standing
cases where the catheter can be firmly embedded in the
parenchyma. The catheter in these situations can be extracted
by passing a stylet into the catheter and applying monopolar
cautery to it. As this is being done, the catheter is gently
twirled. Then it can be extracted easily. If the catheter cannot
be extracted by gentle traction (after applying the cautery) or
even without, it is best left behind. Tugging or forceful pulling
of the catheter will result in intracerebral or intraventricular
haemorrhage.[51] Sometimes on tapping the ventricle, the CSF
may be bloody. If this is encountered, the ventricle is gently
flushed with saline.[52] If the CSF becomes clear  (or faintly
xanthochromic), the surgery is continued. Should the CSF
continue to be bloody, the shunt is converted to ventricular
drainage system, and the insertion is performed later.
When using a connector in the system, the two ends of the
catheters should be in contact. Fibrous tissue will develop
if the connector is exposed, and revision will be rendered
difficult [Figure 4].
The packaging of the system is also essential. For example, if
the proximal ventricular catheter is kept coiled, that catheter
c
Figure 3: (a) Ventricular catheter too long. (b) Ventricular catheter properly placed.
(c) Checking length of ventricular catheter to be placed
may not be used because the implanted catheter may coil up
inside the brain, leading to malfunction of the shunt.
In neonates and very young children, the burrhole should be
placed higher than the usual site. Higher placement may be
beneficial because as the child grows, there will be a tendency for
the burrhole to “move” inferiorly, leading to shunt malfunction.
Pseudo cysts in the abdomen and CSF ascites are frequently
the result of sepsis. Hence, in the event of abnormal collection,
chronic and indolent infections have to be ruled out.[53] CSF
ascites can also occur if shunting is done for optochiasmal
gliomas.[54] In this situation, a ventriculoatrial shunt or ETV
(if feasible) is a better option.[53] If a ventriculopleural shunt
is done, the child may develop hydrothorax and respiratory
distress, and it is best not done unless there is no choice.
The loculated CSF collections can be contained in a true cyst
with walls or between matted bowel loops. These have to be
treated as a case of infection until proven otherwise.[53]
In an analysis, Sekhar et al.[55] found the catheter can get blocked
by cotton fibres from cottonoid patties, hair, or even talc used
in gloves. So it will be prudent to remove all loose hairs and
not use cottonoid patties or talc powder of the gloves.
The problem in a ventriculoatrial shunt is the inability to cannulate
the vein. It is commonly taught that the common facial vein is used.
However, in children, it will be difficult (or impossible) because of
the small size of the vein. In this situation, the internal jugular vein

S498 Neurology India | Volume 69 | Supplement 2 | November-December 2021

 Balasubramaniam: Shunt complications
a
b Pediatr 2016;17:382‑90.
Figure 4: (a) Open ended abdominal catheter obviates distal block. (b) Exposed
connector permits fibrous tissue in growth making revision difficult
can be used. A purse‑string suture is placed on the outer wall of the
vein, and a venotomy is done. The catheter is introduced through
this opening, and the suture is tightened. Optimal placement of the
distal end in the right atria can be checked by using fluoroscopy
using a C‑arm, contrast ventriculogram or transesophageal echo
(probe is placed at the beginning of surgery). Should the catheter
tip be situated too deeply within the right atrium or ventricle, it can
cause arrhythmias secondary to direct irritation of the sinoatrial
and/or atrioventricular nodes, with premature ventricular
contractions being the most commonly observed arrhythmia.
Which Shunt To Use?
The choice of the shunt concerning the opening pressure can be a
bit of confusion to many, particularly those starting in practice. The
author follows a simple protocol of using a low‑pressure system
in infants and neonates. In older children, if the fontanelle is open,
again, a low‑pressure system is used in older children with closed
fontanelle, tumours, or those with papilloedema medium pressure
system. The author has never used a high‑pressure system.
There is no evidence to show that one system is superior
to another.[1,3,10] So the choice is dictated by the surgeon’s
experience, familiarity and availability.[8]
In addition, working knowledge of the other systems will help
if the child has the initial shunt placed in another institution.
Conclusions
Shunts are mechanical systems implanted in a biological
system, and hence it is prone to malfunction. Therefore, some
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S499
problems cannot be avoided, but measures can be taken to
minimize their occurrence. A common saying is ‘All shunts
are created equal, and some are NOT more equal than others’.
The surgeon should use the shunt which works best in
his/her hands. Symposia have been held on shunt problems
and books have been written on this topic.[56] The jury is still
out to decide how to best stay away from trouble.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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49. Baskin JJ, Manwaring KH, Rekate HL. Ventricular shunt removal:
The ultimate treatment of the slit ventricle syndrome. J Neurosurg
1998;88:478‑84.
50. Kemp J, Flannery AM, Tamber MS, Duhaime AC, Pediatric
Hydrocephalus Systematic Review, Evidence‑Based Guidelines
Task Force. Pediatric hydrocephalus: Systematic literature review
and evidence‑based guidelines. Part 9: Effect of ventricular catheter
entry point and position. J Neurosurg Pediatr 2014;14(Suppl 1):72‑6.
51. Becker DP, Nulsen FE. Control of hydrocephalus by valve‑regulated
venous shunt: Avoidance of complications in prolonged shunt
maintenance. J Neurosurg 1968;28:215‑26.
52. Cast IP, Schurr PH. Experience in the use of ventriculoatrial shunts
with the Pudenz valve. Dev Med Child Neurol Suppl 1969;20:71‑4.
53. Salomao JF, Leibinger RD. Abdominal pseudocysts complicating
CSF shunting in infants and children. Report of 18 cases. Pediatr
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Neurosurg 1999;31:274‑8. 55. Sekhar LN, Moossy J, Guthkelch AN. Malfunctioning

54. Gil Z, Beni‑Adani L, Siomin V, Nagar H, Dvir R, Constantini S. ventriculoperitoneal shunts. Clinical and pathological features.
Ascites following ventriculoperitoneal shunting in children with J Neurosurg 1982;56:411‑6.
chiasmatic‑hypothalamic glioma. Childs Nerv Syst 2001;17:395‑8. 56. Choux M. Shunts and Problems in Shunts. Karger; BASEL: 1982.

Neurology India | Volume 69 | Supplement 2 | November-December 2021 S501

 Review Article

Video Avaliable on:

www.neurologyindia.com Endoscopic Third Ventriculostomy ‑ A
Access this article online
Review
Quick Response Code:
Yad Ram Yadav, Jitin Bajaj, Shailendra Ratre, Nishtha Yadav, Vijay Parihar1,
Narayan Swamy, Ambuj Kumar, Ketan Hedaoo, Mallika Sinha

Abstract:
Background: Endoscopic third ventriculostomy (ETV) has become a proven modality for treating obstructive
Website: and selected cases of communicating hydrocephalus.
www.neurologyindia.com
Objective: This review aims to summarize the indications, preoperative workup, surgical technique, results,
DOI: postoperative care, complications, advantages, and limitations of an ETV.
10.4103/0028-3886.332253 Materials and Methods: A thorough review of PubMed and Google Scholar was performed. This review is
based on the relevant articles and authors’ experience.
Results: ETV is indicated in obstructive hydrocephalus and selected cases of communicating hydrocephalus.
Studying preoperative imaging is critical, and a detailed assessment of interthalamic adhesions, the thickness
of floor, arteries or membranes below the third ventricle floor, and prepontine cistern width is essential. Blunt
perforation in a thin floor, while bipolar cautery at low settings and water jet dissection are preferred in a
thick floor. The appearance of stoma pulsations and intraoperative ventriculostomography reassure stoma
and basal cistern patency. The intraoperative decision for shunt, external ventricular drainage, or Ommaya
reservoir can be taken. Magnetic resonance ventriculography and cine phase‑contrast magnetic resonance
imaging can determine stoma patency. Good postoperative care with repeated cerebrospinal fluid drainage
enhances outcomes in selected cases. Though the complications mostly occur in an early postoperative
phase, delayed lethal ones may happen. Watching live surgeries, assisting expert surgeons, and practicing
on cadavers and models can shorten the learning curve.
Conclusion: ETV is an excellent technique for managing obstructive and selected cases of communicating
hydrocephalus. Good case selection, methodical technique, and proper training under experts are vital.
Key Words:
Cerebral ventricle, cerebral ventricles/surgery, cerebrospinal fluid shunts, endoscopic third ventriculostomy,
endoscopy, hydrocephalus, surgical procedures, ventriculocisternostomy, ventriculostomy

Key Message:
Endoscopic third ventriculostomy is a good technique for obstructive and selected cases of communicating
hydrocephalus. It can be combined with other ventricular procedures. The outcome depends on proper case
selection, the surgeon’s experience, and good postoperative care.

E ndoscopic third ventriculostomy (ETV)

has become a recognized modality for
managing obstructive hydrocephalus.[1-4] It can
review is also based on a personal experience
of over 4000 neuroendoscopic surgeries and
over 1000 ETV procedures.
be used in selected cases of posthemorrhagic and
Departments of postinfective hydrocephalus (bulging of anterior Indications
Neurosurgery and and inferior walls of the third ventricle and Obstructive hydrocephalus is the ideal indication
1
Neuroradiology, chronic stages), albeit with poor success rates. for ETV, with congenital or acquired aqueduct
NSCB Medical ETV procedures have also increased in recent stenosis showing the best results.[4] Other ones
College, Jabalpur, times compared to shunt surgeries.[5] include communicating hydrocephalus with
Madhya Pradesh, India inferior bulging of floor and forward bowing of
This is a narrative review based on a PubMed anterior wall of the third ventricle. Slit ventricle
Address for search using the keyword “Endoscopic third syndrome with upward ballooning of the floor of
correspondence: ventriculostomy.” All the 1410 articles were
Prof. Yad Ram Yadav, analyzed along with their cross‑references. This
Director Superspeciality How to cite this article: Yadav YR, Bajaj J, Ratre S,
Hospital, NSCB This is an open access journal, and articles are distributed under the terms Yadav N, Parihar V, Swamy N, et al. Endoscopic
Medical College, of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 Third Ventriculostomy - A Review. Neurol India
Jabalpur ‑ 482 003, License, which allows others to remix, tweak, and build upon the work 2021;69:S502-13.
Madhya Pradesh, India. non‑commercially, as long as appropriate credit is given and the new
creations are licensed under the identical terms. Submitted: 21-May-2021   Revised: 28-Aug-2021
E‑mail: yadavyrns@gmail. Accepted: 22-Sep-2021   Published: 11-Dec-2021
com For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com

S502 © 2021 Neurology India, Neurological Society of India | Published by Wolters Kluwer - Medknow
 Yadav, et al.: Endoscopic third ventriculostomy
the third ventricle is also valid.[6] ETV can be safely performed
in the chronic phase of TBM,[7-9] whereas it is difficult in acute
stages. Lack of cisternal exudates, chronic symptoms, and
long‑term antitubercular therapy have good outcomes.[7,10]
Long‑standing overt ventriculomegaly in adults,[11] idiopathic
intracranial hypertension (ventricles not completely slit like),[12]
and normal pressure hydrocephalus (NPH) (anterior and
inferior third ventricle wall bulging)[13] have also shown good
results with ETV; however, the evidence to use ETV in NPH
in Cochrane Database are inconclusive and of low quality.[14]
ETV is indicated in a failed shunt[15-17] and as a salvage procedure
in recurrent shunt malfunction or infection.[18] Though effective,
ETV is inferior to flexible endoscopic transventricular
transforaminal Magendie and Luschka foraminoplasty, open
suboccipital craniotomy and ventriculo‑peritoneal shunt in
the fourth ventricle outlet obstruction.[19] ETV is also helpful
in fourth ventricle neurocysticercosis (NCC).[20-22]
ETV and biopsy can be performed through a single burr
hole.[23-25] Combined rigid‑flexible endoscope is useful for
ETV and biopsy. ETV has been indicated in hydrocephalus
associated with posterior fossa lesion, cerebellar infarct without
significant brain stem compression, and cerebellopontine angle
tumor. Simultaneous ETV and biopsy of the basal cisterns help
to diagnose basal meningitis.[26]
ETV and clot evacuation[27,28] are useful in intraventricular
hemorrhage (IVH). ETV is effective in full‑term, normal birth
weight infants[29] and Chiari I with or without syringomyelia.[30]
Repeat ETV can be considered in ETV failures.[31,32] ETV reduces
the number of shunts by converting several cavities into one in
multiloculated hydrocephalus. Endoscope helps in converting
a multiloculated cavity into a single cyst and aids in endoscopic
guided ventricular catheter insertion. Majority (about 90%)
of multiloculated hydrocephalus patients remain shunt
dependents, and endoscopy reduces the shunt revision rate
from 2.9 per year to 0.2 per year. ETV is possible in about
10% cases in these patients. It can also perform additional
procedures such as a cyst or membrane fenestration, septum
pellucidotomy, foraminoplasty, and aqueductoplasty. [33]
Hydrocephalus in craniosynostosis is another indication of
an ETV.[34]
Preoperative workup and patient selection
Magnetic resonance imaging (MRI) provides better information
as compared to a computed tomography (CT) scan in
hydrocephalus. Favorable lateral, third ventricle, and cistern
anatomy generally reassure an ETV success [Table 1].
Midsagittal MRI can detect position and indentation of the
basilar artery and other vessels in the third ventricle floor. ETV
is easy in a spacious prepontine cistern with sufficient distance
between the basilar artery and dorsum sellae. Paramedian
posterior communicating arteries predispose for bleeding.
Three‑dimensional (3D) sampling perfection with application
optimized contrasts using different flip angle evolution (SPACE),
balanced steady‑state free precession (BSSFP) (with and
without cine), 3D constructive interference in steady
state (CISS), and phase‑contrast MRI can delineate the
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S503
Table 1: Radiological factors favoring ETV success
Radiological factors favoring ETV success
Sufficiently large lateral and third ventricles
Enlarged Foramen of Monro
Absence of large interthalamic adhesions
Thin third ventricle floor
Third ventricular floor bowing downwards
Sufficient space between the basilar artery and dorsum sellae
No abnormal vessel below the floor of the third ventricle in or near
the midline
Reasonable distance between posterior communicating artery from
the midline
Knowledge about the presence of the Liljenquist or other
membranes in the prepontine cistern
Patent prepontine and other basal cisterns (can be determined by
early stroke volume in cine phase‑contrast MRI)
Absence of basal exudate
Patent distal cerebrospinal fluid (CSF) pathways beyond the basal
cisterns (patent subarachnoid spaces and proper CSF absorption
can be determined by low lumbar outflow resistance or ventricular
outflow resistance)
blockage site preoperatively. 3D SPACE sequence has a
high‑diagnostic yield than a conventional MRI. BSSFP and
dynamic imaging with BSSFP cine allow visualization of
pulsatile structures in cerebrospinal fluid (CSF) space, which
is poorly observed in conventional MRI. 3D CISS imaging
technique has high CSF‑to‑aqueduct contrast and can provide
third ventricular floor thickness, aqueductal anatomy, and
cause of obstruction.[35] 3D CISS can also identify basilar arteries
and the stoma in the third ventricle floor. Cine sequences can
delineate the CSF movement.
The outward displacement of the third ventricular floor,
lamina terminalis, and pineal recess can point toward an
abnormal pressure gradient across them.[36] Preoperatively,
the downward bulge of the floor indicates a good outcome
regardless of the ETV success score (ETVSS).[37] Postoperatively,
a reduction in the displacement is a critical finding for success.
Third ventricle changes precede the decrease in lateral
ventricular size. Reversal of upward ballooning of third
ventricular floor in slit ventricular syndrome (due to higher
pressure in extraventricular spaces compared to ventricle) after
a lumbar puncture is a good candidate for ETV.
3D‑driven equilibrium radiofrequency reset pulse (DRIVE)
sequence and multiplanar reformat are effective modalities to
determine Liliequist or other membranes. Similarly, the FIESTA
imaging can show open or obstructed cisterns.
Early stroke volume in cine phase‑contrast MRI reveals the
status of basal cistern. Spatial saturation‑prepared cine PC‑MRI
can investigate CSF flow by eliminating artifacts due to the
basilar artery. Good CSF flow in basal cistern alone does not
ensure ETV success, and the further patent pathway is also
significant.[38]
Lumbar or ventricular outflow resistance can confirm patent
subarachnoid space (SAS) and adequate CSF absorption.
A resistance of less than 13 mm Hg/ml/min to CSF outflow
ensures a good outcome;[39] however, high resistance does not
 Yadav, et al.: Endoscopic third ventriculostomy

always preclude satisfactory outcomes as enlarged ventricles

may also compress SAS. Such cases may also show good
outcomes.

Surgical technique
ETV has been described in previous publications.[2] Only a few
surgical nuances will be discussed here.

A correct burr hole position is critical. Image guidance[40] or a b

a line extending from interpeduncular cistern to foramen of
Monro (FOM) on to the skull in the sagittal plane MRI are
helpful. The burr hole should be 3 cm away from the midline. It
should be related to the coronal suture of the midline (bregma)
as the suture curves away anteriorly. Failure to understand
it may result in suboptimal burr hole placement and risking
brain injury.[41] The burr hole is generally made on the right
side in symmetric ventricles or on the small‑ventricular side
in asymmetric one for easy perforation of septum pellucidum.
Simultaneous ETV and tumor biopsy for pineal or posterior
third ventricle tumors are possible using two[42] or single burr
holes (in large FOM using rigid endoscopy eliminating the
need for a flexible scope).[43] The transchoroidal approach can
enlarge FOM for ETV and biopsy. A slightly larger sheath
or peel‑away sheath is used to enable repeated insertion of
scope, easy outflow of irrigation fluid, and copious irrigation
in hemorrhage. Lactate fluid irrigation, under normal body
temperature and normal pressure, allows better visualization
and navigation of the endoscope into ventricles.
Although a telescope holder is not mandatory, it is useful in
long surgeries to prevent fatigue. A supported telescope holder
with a loose knob decreases wastage of time in locking and
unlocking.[44] A large ventricle can be entered easily. In slit
ventricles, the shunt catheter is ligated at the clavicle level and
the third ventricular dilation is allowed to make its transverse
diameter ≥5 mm.[45] Stereotactic guidance may also be taken.
The pediatric size rigid scope or fiber endoscope is used. The
average success rate of ETV in slit ventricle is 83%.[45] A good
knowledge of endoscopic anatomy is vital to perform a safe
ETV.[46]
A proper trajectory allows entering the ipsilateral lateral
ventricle at FOM. The navigation or directing the trajectory
toward the external ear in the sagittal plane and slightly medial
in the coronal plane achieves it. With a wrong entry, a significant
tilt toward FOM should be avoided to prevent cortical
injury [Figure 1]. The confluence of thalamostriate vein, septal
vein, and choroid plexus marks the ipsilateral FOM [Figure 2],
where septal and thalamostriate veins are on the medial and
lateral side respectively. Entry to the contralateral ventricle may
result in bilateral fornix injury [Figure 1]. A FOM of 7 mm or
larger allows safe entry for a normal size rigid scope. In cases
with small FOM, a flexible or pediatric scope is useful, or a
rigid scope stationed very close to FOM can perform the ETV.
Infundibular recess, mammillary bodies, location of the basilar
artery, and massa intermedia are critical structures. A thick
and prominent massa intermedia and narrow tuber cinereum
might be present in 40% of myelomeningoceles. Large and
multiple interhypothalamic adhesions (IHA), although rare,
may hinder access to the third ventricular floor or increase
c d
Figure 1: (a) MRI sagittal image showing correct (shown as 1), wrong anterior (2),
and wrong posterior (3) trajectory in the lateral ventricle; (b) coronal image showing
correct (1) trajectory through the ipsilateral foramen of Monro in the third ventricle,
wrong too lateral trajectory (2), and wrong trajectory (3) through contralateral
Monro; (c) sagittal image showing correct (1), wrong anterior (2), and wrong
posterior (3) trajectory in the third ventricle; and (d) two different trajectories for
endoscopic third ventriculostomy (1), and biopsy (3), and single trajectory (2) can
be planned between 1 and 3 when Monro is large
the risk of bleeding and hypothalamic injury, which may need
either abandonment of ETV or dividing the IHA.[47]
In a small FOM and when a rigid scope is used with a single
burr hole, one should avoid linear movements in the third
ventricle or perform slow movements up to 5 mm anterior
or posterior. Two burr holes or a combination of rigid and
flexible scope are useful. Steep third ventricle floor and small
prepontine space may pose difficulties in ETV.
ETV in posterior fossa tumors is difficult due to compressed
prepontine space and insufficient distance between dorsum
sellae and basilar artery. The third ventricle perforation in such
cases should be made in the midline on the dorsum sellae by
rotation movement of grasping forceps. For laterally placed
tumor such as a cerebellopontine angle lesion, the surgeon
needs to be extracautious as the brain stem and midline is
displaced anteriorly and to the opposite side. In such cases,
the midline should be taken in reference to the mammillary
bodies. Once the third ventricle floor is perforated, CSF enters
the cistern making it prominent, which can be further dilated
with balloon or ventriculostomy forceps.
In opaque floor, a microvascular doppler probe is helpful. When
doppler is unavailable, gentle probing by bipolar forceps tip can
identify dorsum sellae, and fenestration is made in the midline
just posterior to it. The transparent site anterior to the basilar
artery and between mammillary bodies and infundibular
recess is the ideal site for fenestration. A blunt fenestration
without thermal or electric energy avoids vascular injury in
the floor. Bipolar cautery at low setting [Video 1 and Figure 2]
and water jet dissection are safe and effective on a tough and
opaque floor.[48] Laser and ultrasonic contact probe assistance

S504 Neurology India | Volume 69 | Supplement 2 | November-December 2021

 Yadav, et al.: Endoscopic third ventriculostomy

a b c

d e f

g h i
Figure 2: Endoscopic images showing (a), foramen of Monro identified by the confluence of choroid plexus (star), septal vein (arrow facing down), and thaloamostriate
vein (arrow facing up); (b) bipolar forceps trying to perforate blunt and tough third ventricle floor which is difficult to penetrate; (c) cauterization of floor by low setting current by
bipolar; (d) dilatation of stoma after blunt perforation using ventriculostomy forceps; (e-g) perforation and dilatation of Liliquist membrane; (h) closed ventriculostomy forceps
facing bare basilar artery; and (i) naked basilar artery with terminal branches

are also useful in a third ventriculostomy. Cauterizing the

stoma margins may prevent reclosure of it.

After careful inspection of the interpeduncular cistern, a French

Fogarty catheter or ventriculostomy forceps are effective
to dilate the stoma [Figure 2]. One should avoid pulling an
inflated Fogarty catheter or ventriculostomy forceps to prevent
vascular trauma. The opening of membranes should be under
direct endoscopic visualization and be in the SAS, which is
dorsal to the clival line, and not in the subdural space.[49] The
naked basilar artery in association with good stoma pulsation
suggests a successful ETV.

Intraoperative decision to continue with ETV[50,51] needs for
shunt[52,53] or external ventricular drainage (EVD)/Ommaya
reservoir[54] has been described in Figure 3. Usage of an EVD
may have a negative effect on the chance of ETV success as it
may lead to insufficient flow across the stoma and predisposing
for its closure. However, it is prudent to put an EVD when
the surgeon has an intraoperative doubt of success with
insufficient reasons for converting to a shunt. The surgeon’s
impression and the results of intracranial pressure (ICP)
monitoring offer approximately the same predictivity for
a successful ETV.[50] There was a good correlation between
preoperative ETVSS and a bare intraoperative basilar artery.[51]
The folding sign predicts a successful ETV when the LM
is sufficiently opened.[55] A folding sign is a formation of a
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S505
Figure 3: Flow chart showing intraoperative decision for endoscopic
third ventriculostomy, external ventricular drain, or Ommaya
reservoir. (ETV = endoscopic third ventriculostomy)
sequence of longitudinal folds at the tectal region (running
from the mammillary body to the aqueduct), which is easily
detectable intraoperatively in about 40% patients and is an
indicator of penetration of both the third ventricle floor and the
Liliequist or other underlying membrane during operation. It
may vary from faint to obvious folds. Folding sign is likely to
emerge in a patient with long‑standing hydrocephalus, such
as congenital one, rather than in a patient with acute‑onset
hydrocephalus such as that caused by intraventricular
hemorrhage.
 Yadav, et al.: Endoscopic third ventriculostomy
It could be due to resolution of the pressure gradient between
the ventricle and the cisterns. The elastic properties of the
posterior wall of the third ventricle allows to fold after release
of chronic distension.
In abnormal anatomy, inadequate interpeduncular SAS, and
unsatisfactory floor fenestration, a flexible endoscope may
aid in perforating lamina terminalis through a subfrontal
or transventricular transforaminal approach. [56] Similarly,
quadrigeminal cistern fenestration from the lateral ventricle
or third ventricle is also an effective technique.
Indocyanine green angiography can be helpful in delineating
aberrant vessels in opaque floors or reoperations and choosing
a biopsy point. Stereotactic techniques and image guidance
can decrease complications, especially for beginners. Stented
ETV is useful in high risk of stoma closure due to tumorous
infiltration of the floor. It is fixed to the burr hole reservoir to
prevent migration and retrieval.
The addition of choroid plexus coagulation (CPC) improves
the ETV outcome especially in infants, postinfective,
and posthemorrhagic hydrocephalus. It is also useful in
infants with complex multiloculated, myelomeningocele
hydrocephalus, high risk of complications after shunt,
and in choroid plexus hyperplasia, where follow‑up
is difficult due to geographical and/or socioeconomic
constraints. CPC stabilizes macrocephaly in approximately
40% of infants with severe congenital hydrocephalus and
hydranencephaly.[57] Patients with gradually progressive
hydrocephalus and lacking septum pellucidum (technically
easy by single burr hole) are the appropriate candidates for
CPC.[58]
Results
ETV success varies from 40 to 87%, depending on proper
case selection, the experience of the surgeon, and proper
postoperative care [Figure 4]. Table 2 shows our results from
1042 procedures. ETV not only works as an internal shunt
but also restores the pulsatility of the ventricular walls.
Quality of life (QOL) has become a critical factor after any
intervention. Seizures, repeated interventions, communicating
hydrocephalus, and prior shunts result in poor QOL after an
ETV.[59]
Figure 4: Line diagram showing factors (proper case selection, intraoperative
findings, surgeon experience, proper postoperative care) influencing outcome after
endoscopic third ventriculostomy
S506 Neurology India | Volume 69 | Supplement 2 | November-December 2021
Different ETVSSs, suggested by Kulkarni, CURE Children’s
Hospital of Uganda, are available. These utilize etiology, age,
CPC, type of hydrocephalus, and previous shunt placements
for determining outcomes. The ETVSS predicts the outcome
of ETV, which can be used in the decision making and
prognostication. Artificial neural network analysis is another
modality to determine outcomes in children.[60] While the
ETVSS shows good prediction, it tends to underestimate.[61]
Failure to improve after ETV depends on many factors and is
not always due to stoma block [Figure 5].
ETV is effective in all age groups including full‑term normal
birth weight infants.[29] Though some studies have reported
poor results in infants younger than 3 months, the effectiveness
has been related to etiology. ETV success was 40–50% in infants
and children managed after fetal myelomeningocele repair.[62]
A third ventriculostomy provides an effective treatment for
hydrocephalus associated with Chiari I malformation and
intraventricular NCC.[20-22] Third ventriculostomy and cyst
removal are possible with a single precoronal burr hole using
a rigid scope and a curved tip angiographic catheter,[21] and
with transventricular, transaqueductal “scope‑in‑scope”
technique.[22]
ETV in postmeningitic hydrocephalus is technically demanding
in the acute stage of the disease; the success rate is poor, and
therefore should be avoided. Whereas in the chronic phase
of the disease, it is safe to perform and is very effective. Poor
ETV success has been found in TBM (58–80%) as compared
to aqueductal stenosis.[63] ETV is likely to fail in advanced
clinical grades, basal cisterns with dense adhesions, and an
unidentifiable floor. The primary reasons for bad outcomes
after an ETV are described in Figure 6. Complex hydrocephalus,
with a combination of obstructive and communicating
components, and cerebral infarcts are the main ones. The
addition of a lumbo‑peritoneal (LP) shunt improves the
outcome in raised ICP after ETV.[10]
The ETV is effective after a failed shunt.[64] Age is not a
contraindication for secondary ETV. The success rate of
secondary ETV varies between 51 and 100%, and a pooled
success rate from literature is 65.1% (598 successful ETV out
of 918 patients). Most failures occur early after primary ETV,
whereas it is delayed in secondary.[65] Shunt ligation and
removal are associated with good ETV success and fewer
Figure 5: Flow diagram showing various causes of failure to improve after surgery
and how to manage them
 Yadav, et al.: Endoscopic third ventriculostomy

infections due to hardware. The flow through a shunt may Complications

increase chances of stoma block; however, it should be taken
out only in the absence of adhesions or neovascularization.
Though ETV has initial high failure rates compared to
shunts. [66] Table 3 shows the comparison between shunt
and ETV outcomes. Long‑term results are similar or even
better for ETV in most series.[66,67] Initial results of shunts
in international infant hydrocephalus study were superior
to ETV.[68] Shunts may also have a better cognitive function
than ETV.[69]
Overall complication rate varies from 8 to15% according to the
etiology. Misplacement of the fenestration and learning curve are
the main reasons for severe complications. Complications could
be permanent and temporary, intraoperative, early (<1 month),
and late postoperative (>1 month) types. Intraoperative
and early complications include hemorrhage (cortical,
ventricular, and cisternal vessels), neural injury (fornix,
third cranial nerve, hypothalamus, and midbrain), subdural
collections, pneumoventricle, hyponatremia, seizures, delayed
awakening, bradycardia, hypothalamic dysfunction (diabetes

Table 2: Success rate and complication in ETV in present series

Etiology with number of patients in bracket: Number of successful ETV with percentage in bracket:
Congenital aqueduct stenosis (n=523) 439 (83.9%)
Chronic stage of TBM (n=187) 135 (72.2%)
Posterior third ventricle lesion (n=49) 35 (71.4%)
Midline posterior fossa tumor (n=23) 18 (78.3%)
Cerebello‑pontine angle tumor (n=29 22 (75.9%)
Myelomeningocele and other spinal dysraphism (n=43) 28 (65.1%)
NPH (n=18) 11 (61.1%)
Slit ventricle syndrome (n=9) 7 (77.8%)
Others (Dandy‑Walker malformation, syringomyelia with or without Chiari 17 80.9%
malformation Type I, encephalocele, craniosynostosis, cerebellar infarct, etc. (n=21) 712 78.9%
Total (n=902)
Secondary ETV: Successful ETV with percentage:
Shunt malfunction (n=67) 48 (71.6%)
After failed ETV (n=73) 62 (84.9%)
Total (n=140) 110 (78.6%)
ETV in infants (n=274) Successful=205 (74.8%)
ETV in more than 1 year of age (n=628) Successful=507 (80.7%)
Type of complications: Number of patient with percentage:
Intraoperative hemorrhage, 34 (3.3%)
Permanent morbidity (neurological 17 and hormonal 4) 21 (2.0%)
CSF leak, 14 (1.3%)
Central nervous system infections, 12 (1.2%)
postoperative intracranial hematomas, 8 (0.8%)
Intraoperative neural injury, 3 (0.3%)
Early postoperative mortality, 3 (0.3%)
Delayed sudden death 1 (0.1%)
Total complications 81 (7.8%)

Table 3: Comparison between shunt and ETV outcomes

Variable Shunt ETV
Symptom improvement Equal Equal
Reduction in ICP Faster Gradual
Overdrainage and subdural hematoma Possible Less likely
Metastasis/spread of tumor/infection extracranially Possible Absent
Possibility of an additional procedure like a biopsy (which may Absent Possible
help in diagnosis)/cyst or septum fenestration
Infections Higher than ETV Lower than a shunt (more benign course and
generally controlled by antibiotics alone
Permanent hardware and its related complications Present Absent
Failure rates Lower in early period, but Lower overall after 3 months
overall more in long term
Reoperation Higher Lower
Duration of surgery Longer Shorter
Postoperative stay Longer Shorter

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 Yadav, et al.: Endoscopic third ventriculostomy

insipidus, lack of thirst, amenorrhea), and hyperthermia. Late
complications include reclosure of the stoma, weight gain,
precocious puberty, etc. Details about the causes of various
complications and their avoidance have been discussed in
Tables 4-6.[70-72]
A repeat ETV can also be done and has about 80% success rates
compared to first attempts. Repeat ETV success is influenced by
ETVSS factors such as age,[73] etiology,[73] and previous shunt.[73]
Longer time to failure  (more than 3  months) after the first
procedure,[31,74] closed stoma by translucent/semitransparent
membranes,[32] postinfectious etiology,[74] and prior CPC had
significantly better outcome.[74]
Proper training on cadavers, [75] models, [76] and low‑cost
simulation models,[77] attending live workshops, and simpler
case selection can shorten the learning curve.[44] Understanding
various endoscopic nuances and techniques to deal with
limitations of endoscopy such as blind area, triangulation,
and introducing instruments in a limited area is critical.[78]
Recently, various online learning resources have come. These
are especially useful for young and resource‑limited countries.
Some of these platforms include WFNS Young Neurosurgeons
Forum Stream, the Neurosurgical Atlas, European Association
of Neurosurgical Societies Academy, the Rhoton Collection, etc.
Late sudden death is a rare complication of ETV, and patients
and caregivers should be informed about it. A false sense of
reassurance after a successful ETV should be avoided. The
mechanism of late sudden death is unclear and could be due
to sudden stoma closure and hydrocephalus. The deterioration
can also occur long after the ETV closure. An indwelling
ventricular access device may prevent it.[79,80] The incidence
of sudden death is probably less than 0.1%.[81] Absence of
perimesencephalic cisterns with severe hydrocephalus
even in an asymptomatic patient points toward impending
neurogenic cardiorespiratory failure. These cases should
undergo emergency ventriculostomy or shunt with any new
onset neurologic symptom or sign.[82]

Postoperative radiological evaluation and care after ETV

The outcome after ETV also depends on proper postoperative
care [Figure 4]. Clinical improvement is more reliable as
compared to any radiological parameters such as Evans’ index,
frontal horn, and third ventricular diameter. MRI provides
more information about a decrease in ventricular size and
stoma patency as compared to a CT scan. Optic nerve sheath
diameter and disk bulging reduction on MRI is an indicator
of success after surgery.

A gradual decrease in stoma size in the first 3  months of

Figure 6: Flow diagram showing various treatment options in tuberculous postoperative MRI is an indicator of ETV failure.[83] A decrease
meningitis with hydrocephalus. (CSF = cerebrospinal fluid, ETV = endoscopic in ventricle size occurs very slow in the first few months, is
third ventriculostomy, LP = lumbar peritoneal, Re = repeat, TBM = tuberculous more prominent in acute forms of hydrocephalus, and for the
meningitis, VP = ventriculo‑peritoneal) third ventricle compared to the lateral ventricles. Measurement

Table 4: Causes of bleeding complications during endoscopic third ventriculostomy, how to avoid it, and the
treatment
Causes of Intraventricular bleeding How to avoid complication Treatment of complication
Excessive side movements due to Avoid wrong entry into the lateral Bleeding usually stops spontaneously with copious irrigation by warm
wrong entry site in the lateral ventricle ventricle, refrain significant side Ringer’s solution,
movement in ventricles Inflating balloon catheter or gently keeping instrument on bleeding
Catching vessel or perforator in balloonPartially retract the forceps or point rather than removal of balloon or instrument
or ventriculostomy forceps and pulling balloon into the third ventricle Forceful irrigation may allow visualization of the bleeding site for
it before opening it fully bipolar coagulation.
Direct ventricular access by the scope, Use brain cannula Maintain ventricular access in severe bleeding by keeping sheath
and use of a sharp‑edged sheath within the field rather than pulling it back. Can station it in lateral
Repeated introduction of scope without Use peel away or other sheath ventricle.
using peel‑away or other sheath Withdraw endoscope about 1‑2 cm away from the distal end of the
Thick and inflamed floor leading to Perforation on dorsum sellae. sheath; sheath tip can compress the bleeding vessel, and the small
increased vascularity Careful use of low‑current cavity formed between the sheath tip and endoscope tip helps in
and stretching of floor bipolar in thick floor, using water better visualization of bleeding point.
dissection in thick and opaque Fluid can be replaced by air (dry field) to help coagulation of the
third ventricle. bleeding point
Sharp perforation of thin third ventricle Prefer blunt dissection in thin Use a tubular retractor with an air medium when significant bleeding
floor floor is not controlled by any of the techniques.
Blood trickling from burr hole site into Proper hemostasis before Once bleeding is stopped, intraventricular blood should be evacuated.
the ventricle entering the ventricle Ventricular drain in residual oozing
Removing flexible scope in curved tip Removal of flexible scope in a
position neutral position

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 Yadav, et al.: Endoscopic third ventriculostomy

Table  5: Causes of various complications  (cerebrospinal fluid leak, blocked stoma, hypothalamic damage,
delayed awakening, fatigue, and lack of precision and bradycardia) during endoscopic third ventriculostomy
(ETV) and how to avoid these complications
Complications Causes Avoidance of complication
Cerebrospinal fluid leak Raised intracranial pressure (ICP) Proper management of raised ICP
Early suture removal Delayed suture removal
Thin cortical mental Plug cortical opening with AbGel sponge, galeal pericranial flap,
and dural repair in large ventriculomegaly in infants
Large dural or cortical opening Small dural and cortical opening
Blocked Stoma Inadequate size of the stoma Larger opening (5 mm or more)
Hemorrhagic obstruction facilitating stoma Proper case selection by avoiding ETV in posthemorrhagic and
closure infective pathology
Presence of unappreciated Lilliquist or other Perforation of membrane bellow third ventricle floor if
secondary membranes present (bare basilar artery)
Elevated cerebrospinal fluid protein and tumor Proper case selection
progression
Regrowth of new arachnoid membrane in infantsAvoid ETV in infants of less than 3 months
Hypothalamic damage Thick floor perforation by blunt instrument Initial use of cautery or sharp instrument to perforate thick floor
causing stretch injury
Ventriculostomy away from the midline Midline ventriculostomy
Delayed awakening Long‑acting anesthesia drugs. Avoid long‑acting anesthesia drugs
High intracranial pressure Avoid raised intracranial pressure (free egress of irrigation fluid
from outflow channel)
Fatigue and lack of precisionUnsupported hand and long surgery Hand support, optimal help of an assistant
Bradycardia Raised intracranial pressure Check that the outflow is open, and the fluid is coming out from
the channel, turn up the volume of the cardiac monitor and keep
the noise down in the theatre, reverse the last action when there
is bradycardia
Use of cold saline irrigation Use ringer lactate at normal temperature
Different osmolarity fluid as compared to plasmaIsoosmolar irrigation fluid (Ringer lactate rather than normal saline)
Forceful and rapid rate of irrigation Slow and normal irrigation without force
Traction on hypothalamus by balloon or forceps Perforation of third ventricle floor by sharp instruments when the
floor is thick to avoid stretching

of postoperative third ventricle floor depression, lamina
terminalis bowing, anterior commissure to tuber cinereum
distance, mamillary body to lamina terminalis distance, and
third ventricular width can predict ETV success. Postoperative
change in callosal angle is higher than other ventricular
parameters.[84] Likewise postoperative infundibular recess
angle reduction [85] and anterior third ventricular height
correlated well with a successful ETV.[86]
Different MRI sequences such as T2 W Turbo Spin Echo images,
3D‑SPACE sequence, time‑resolved 3D MR velocity mapping,
and cine phase contrast can be used in the postoperative
assessment of CSF flow, stoma patency, and noninvasive flow
quantification.
CT or MR ventriculography can be a good indicator of stomal
patency in difficult cases.
Good postoperative care of raised ICP can improve
ETV success. [87] There are some patients (especially
myelomeningocele, ETV after shunt, infants, and young
children, postinfective and posthemorrhagic) who continue to
have raised ICP after an ETV. This could be due to collapsed
SASs after shunt surgery or in children with underdeveloped
SAS. This can also be seen due to scarring of cisterns or SAS
after infection and hemorrhage. Postoperative raised pressure
after ETV could be there due to defective absorption of CSF
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S509
from arachnoid villi. The raised pressure after ETV in all these
patients could be temporary that can be relieved by repeated
lumbar punctures. If the pressure remains persistently raised
even after repeated LP, we consider such cases as failed ETV
and subject them to shunt.[88] The LP shunt can be put in small
size ventricles and is an extracranial procedure. It effectively
controls persistent raised ICP after an ETV.[7,89] The blamed
complication rates such as symptomatic tonsillar ectopia are
not common in our large experience.[90,91]
A monthly clinical surveillance for 3 months and then yearly
for lifelong is needed as late complications, though rare, can
occur. There is no solid data to support rapid MRI surveillance
imaging in ETV, as reported in shunt patients. There was no
reduction in shunt revision or complication rate in patients
with normal imaging findings in the surveillance imaging
group as compared to only the clinical examination group.
Routine surveillance imaging resulted in more revision rate in
asymptomatic patients with abnormal radiological findings.[92]
It is therefore justified to do clinical surveillance only and order
imaging on clinical suspicion of block or other complications.
Advantages and limitations
Simultaneous ETV and tumor biopsy is possible in
marker‑negative pineal tumors,[93] posterior third ventricle
lesion,[94] and near‑mesenchymal aqueductal tumor.[95] ETV
and biopsy can be performed from the ventricle in TBM[7] and
 Yadav, et al.: Endoscopic third ventriculostomy

Table 6: Causes of various complications (failure to perform endoscopic third ventriculostomy, fornix injury, and
hypothermia) during endoscopic third ventriculostomy and how to avoid these complications
Complication Causes Avoidance of complication
Failure to Small foramen of Monro and narrow third ventricle width, less Careful case selection
perform ETV space between the basilar artery and dorsum sellae, small
prepontine space, unusually thick and inflamed third ventricle
floor, large inter thalamic adhesion, upward herniation of the
basilar artery, and its perforators in third ventricle floor
Large and multiple interhypothalamic adhesions (IHA),
although rare, can hinder access to the third ventricular floor
Fornix injury Small foramen of Monro Proper case selection with enlarged foramen of Monro, use
of small size scope, shrinkage of choroid plexus by bipolar
coagulation, use of flexible scope, keep scope in lateral
ventricle near fornix, and perforation of the floor using a blunt
instrument from distance
Direct ventricle tap by the sheath Ventricle tap by brain needle avoiding direct entry by the scope
Misdirected brain penetration exceeding 6 cm from burr hole Properly directed brain penetration not more than 5‑6 cm from
burr hole
Flexible scope is removed in curved tip position Flexible scope should be removed in a straight tip position
Wrong entry in the contralateral ventricle Identify ipsilateral ventricle (thalamostriate and septal veins)
Side movement of the telescope in the third ventricle Proper planning of burr hole site, avoiding significant side
movements
Wrong placement of burr hole and incorrect entry third Proper site burr hole as medial as possible decided by
ventricle by too lateral, anterior, or posterior trajectory navigation or individual patient parameters near coronal suture
Hypothermia Frequent in small children and infants Temperature monitoring especially in infants and small children
Large exchanges of irrigation fluid Prewarmed irrigation fluid and judicious use of irrigation fluid
Wetting of drapes Avoid wetting of drapes by using a drainage line connected to
an outflow
Hypothalamic injury Prevention of hypothalamic injury

meninges in basal meningitis, and tumor infiltration.[96] It can
also be combined with fenestration of cysts, perforating the
septum pellucidum, enlarging the FM, and aqueductoplasty.[33]
Simultaneous ETV and IVH removal,[28] fourth ventricle NCC
excision, and arachnoid cyst fenestration are possible. A shunt
can still be performed in failed ETV.
Limitations of endoscopy include a steep learning curve,
two‑dimensional image, proximal blind spot, repeated visual
obscurations, difficult hemostasis, and chances of disorientation.
ETV is inferior to shunt in acute infection, premature infants,
postinfective and posthemorrhagic hydrocephalus. CPC or LP
shunt is required when ETV alone does not work.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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 Review Article

Access this article online

Quick Response Code:
Endoscopic Third Ventriculostomy and
Choroid Plexus Coagulation in Infants:
Current Concepts and Illustrative Cases
Ronnie E Baticulon, Michael C Dewan1
Website:
www.neurologyindia.com

DOI: Abstract:
10.4103/0028-3886.332270
Background: The global burden of pediatric hydrocephalus is high, causing significant morbidity and mortality
among children especially in low‑ and middle‑income countries. It is commonly treated with ventriculoperitoneal
shunting, but in recent years, the combined use of endoscopic third ventriculostomy (ETV) and choroid plexus
coagulation (CPC) has enabled patients to live without a shunt.
Objective: We aim to give an overview of ETV+CPC for the treatment of hydrocephalus in infants, focusing
on patient selection, perioperative care, and long‑term follow‑up.
Methods and Material: We summarize observational studies and randomized trials on the efficacy and safety
ETV+CPC, mainly from Uganda and North America. The equipment needs and operative steps of ETV+CPC
are enumerated. At the end of the article, three illustrative cases of infants who underwent ETV+CPC with
differing outcomes are presented.
Results: The likelihood of success following ETV+CPC is the highest among infants older than 1 month, those
with noninfectious hydrocephalus (e.g., aqueductal stenosis and myelomeningocele), and those previously
without a shunt. Poor outcomes are seen in patients with posthemorrhagic hydrocephalus or evidence of
cisternal scarring. Failure of ETV+CPC most commonly occurs within 3–6 months of surgery.
Conclusions: ETV+CPC is an effective and safe alternative to ventriculoperitoneal shunting in appropriately
selected infants with hydrocephalus. Long‑term studies on functional and neurocognitive outcomes following
ETV+CPC will help guide clinicians in decision making, allowing as many children as possible to attain shunt
freedom.
Key Words:
Choroid plexus coagulation, endoscopic third ventriculostomy, pediatric hydrocephalus

Key Message:
Shunt freedom and favorable neurologic outcomes are achievable in a significant proportion of hydrocephalic
infants treated with endoscopic third ventriculostomy and choroid plexus coagulation.

Department of
E very year, almost 400,000 new cases of
pediatric hydrocephalus are diagnosed
globally.[1] Since the introduction of silicone shunts
of antibiotic‑impregnated catheters have reduced
shunt infection rates to 2–6%, but figures vary
widely across centers.[6,7] To many children, these
Neurological Surgery, in the late 1950s,[2] diversion of cerebrospinal shunt complications pose a life‑long threat to
Vanderbilt University fluid (CSF) to the peritoneal cavity or other distal neurocognitive function and may significantly
Medical Center, sites has been the main surgical treatment for this impair their quality of life.[8,9]
Nashville, Tennessee, disease in most countries. Ventriculoperitoneal
USA, 1Department shunting is an essential skill set among general With the goal of reducing shunt dependency,
of Neurosciences, neurosurgeons and pediatric neurosurgeons there has been renewed interest in the combined
Philippine General alike,[3] and the life‑saving operation may be use of endoscopic third ventriculostomy (ETV)
Hospital, University of performed even in primary hospitals.[4] Despite and choroid plexus coagulation  (CPC) among
the Philippines Manila, advances in shunt technology, however, the infants with hydrocephalus, gaining momentum
Manila, Philippines failure rate during the first year of shunt in the last two decades. While many studies
implantation remains between 20 and 40%.[5] supporting the efficacy and safety of ETV+CPC
Address for
Implementation of shunt protocols and the use
correspondence:
Dr. Ronnie E Baticulon, How to cite this article: Baticulon RE, Dewan MC.
Division of Neurosurgery, This is an open access journal, and articles are distributed under the terms Endoscopic Third Ventriculostomy and Choroid
Philippine General of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 Plexus Coagulation in Infants: Current Concepts and
Hospital, Taft Avenue, License, which allows others to remix, tweak, and build upon the work Illustrative Cases. Neurol India 2021;69:S514-9.
Manila ‑ 1000, Philippines. non‑commercially, as long as appropriate credit is given and the new
creations are licensed under the identical terms. Submitted: 01-Jul-2021 Accepted: 18-Sep-2021
E‑mail: rebaticulon@ Published: 11-Dec-2021
up.edu.ph For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com

S514 © 2021 Neurology India, Neurological Society of India | Published by Wolters Kluwer - Medknow
 Baticulon and Dewan: ETV and CPC in infants
were initially conducted in low‑resource settings in East
Africa, [10‑12] completed and ongoing prospective trials in
North America are helping define the role of ETV+CPC in the
contemporary management of pediatric hydrocephalus.[13‑15] In
this article, we give an overview of ETV+CPC among infants.
Illustrative cases are provided to demonstrate clinical decision
making for pediatric neurologists and neurosurgeons who
intend to incorporate ETV+CPC into their practice.
ETV+ CPC in young infants
The history of ETV and CPC for the treatment of hydrocephalus
has been extensively discussed elsewhere.[2,16,17] In 2005, working
at Cure Children’s Hospital of Uganda (CCHU), Benjamin Warf
published his analysis of 550 children who underwent either
ETV alone or ETV+CPC.[11] These were mostly infants, with
58% of patients having postinfectious hydrocephalus. Warf
showed that among patients less than 1‑year old, the addition
of CPC to ETV increased the proportion of successful treatment
from 47 to 66%. Success was defined as being shunt‑free on
last follow‑up, with a median duration of 9.2 months for
the ETV+CPC cohort. Further, the intervention was more
likely to succeed in infants with hydrocephalus that was not
infectious in etiology, and in those with myelomeningocele.
Subsequent studies in CCHU have demonstrated similarly
good outcomes in patients with aqueductal stenosis,[18] Dandy
Walker complex,[19] encephaloceles,[20] and congenital idiopathic
hydrocephalus.[21]
Driven by these encouraging numbers from Uganda,
neurosurgeons from around the world have since published
their own experiences with ETV+CPC. In Nigeria and Haiti,
success rates of 75%  (out of 20  patients) and 52%  (out of
82  patients), respectively, were reported after 6  months
of follow‑up. [22,23] Among patients that Warf treated in
Boston, 57% did not require any additional surgery for
hydrocephalus at 1 year.[24] In this first ETV+CPC series in
North America, scarring of the prepontine cistern and prior
CSF diversion were demonstrated to be additional predictors
of poor outcome. A more recent prospective study from
the Hydrocephalus Clinical Research Network involving
191 patients demonstrated a 48% success rate for ETV+CPC
at 6 months, only slightly declining to 45% at 18 months.[14]
ETV failure was more likely in patients less than 1 month of
age and in those with hydrocephalus from intraventricular
hemorrhage of prematurity.
How does ETV+CPC work?
In the bulk flow model of CSF circulation,[25] CSF secreted
predominantly by choroid plexus flows within and exits
the ventricular system to reach the intracranial and spinal
subarachnoid space. CSF is subsequently absorbed in the
dural venous sinuses through arachnoid granulations. When
hydrocephalus is obstructive in nature  (e.g.,  aqueductal
stenosis), the rationale behind an ETV is fairly straightforward:
an alternate pathway from the third ventricle to the prepontine
cistern is created, allowing CSF to bypass the obstruction.
However, as studies have shown, ETV alone is often inadequate
for addressing hydrocephalus in young infants.[26,27] This is
presumed to be because of insufficient CSF absorption through
the arachnoid villi in this age group, where other pathways
such as periventricular capillary absorption may play a bigger
role.[28] It is theorized that by cauterizing choroid plexus in
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S515
lateral ventricles, CSF production is reduced while waiting
for absorption pathways to mature, and over time, transition
to adult circulation.[16]
Where these mechanisms fall short is in explaining how good
outcomes have been achieved with ETV+CPC, even when (1)
hydrocephalus is idiopathic, where no obvious anatomic
obstruction is apparent,[21] and  (2) CSF production persists
from residual choroid plexus and extrachoroidal sources such
as ependyma and cerebral capillaries.[28]
Using the hydrodynamic model of CSF,[25] it is postulated
that pediatric hydrocephalus is not just a consequence of
high‑ventricular CSF pressure. Warf proposes that choroid
plexus pulsation is also a significant driver of ventricular
enlargement.[21] Thus, coagulating choroid plexus decreases
these rhythmic, intraventricular forces during the cardiac cycle,
especially important in a young infant whose brain parenchyma
has high compliance. CPC also leads to a consequent reduction
in cerebral venous pressure, thereby increasing capillary
absorption of CSF. In keeping with this mechanism, the ETV
stoma acts as a pulsation absorber, dissipating pulsatile forces in
the ventricular cavity to the basal cisterns. The combined effects
of ETV (“pulsation absorber”) and CPC (“pulsation reducer”)
restore equilibrium between CSF production and absorption
in the infant brain.[21] The goal is a reduction in intracranial
pressure to enable normal brain growth and development.
Identifying ideal patients for ETV+CPC
Whether in East Africa or North America, it is evident from
published literature that the benefits derived from ETV+CPC
vary among subgroups of patients. Thus, the onus is on the
neurosurgeon to identify which infants are suitable candidates
for ETV+CPC. For clinicians, the ETV success score (ETVSS)
developed by Kulkarni and colleagues is a useful and externally
validated tool for estimating the likelihood of success at
6 months following an ETV.[29,30] It considers three patient
factors: age, etiology of hydrocephalus, and prior shunting.
To illustrate, a 6‑month‑old infant with aqueductal stenosis
and no prior shunt has an ETVSS of 70, whereas a 1‑month‑old
infant with communicating hydrocephalus has an ETVSS of
20. Thus, it would be more reasonable to offer ETV+CPC as
primary treatment for hydrocephalus in the former. While a
low ETVSS (≤ 40) does not preclude ETV+CPC, parents must
be counseled so that appropriate expectations are set. It is
important to communicate that there may be a need for early
reintervention particularly within the first 3 months; this risk
is weighed against shunt dependency with its life‑long risk of
multiple shunt revisions.
Neuroimaging is a requisite for safe neuroendoscopy. At the
minimum, a computed tomography (CT) of the brain should be
obtained. It allows the neurosurgeon to establish an etiologic
diagnosis, plot the trajectory for the ETV, identify anatomic
variations, and inspect the thickness of the third ventricular
floor, adequacy of the prepontine space, and the basilar artery’s
position and course. If septations, loculations, and/or abnormal
contrast enhancement are present, a transfontanel ventricular
tap is useful to rule out active infection.
Magnetic resonance imaging  (MRI) of the brain is ideal but
may not always be feasible. T2‑weighted sequences in three
 Baticulon and Dewan: ETV and CPC in infants
planes provide sufficient information, supplemented by sagittal
FIESTA/CISS sequence to show the anatomy of the Liliequist
membrane and any cisternal scarring. If extensive scarring
and/or redundant membranes are seen on MRI, it is prudent
to proceed with VP shunting instead due to the high rate of
ETV failure seen in these patients.[31]
In limited‑resource settings where only an ultrasound
is available, neurosurgeons are advised to proceed with
caution. The third ventricular floor, prepontine space, and
other posterior fossa structures are not clearly delineated on
an ultrasound—especially in cases of severe macrocephaly.
Characteristics known to influence ETV success, which may
otherwise be apparent on MRI, may not be observed until the
time of intraoperative endoscopic inspection. It is reasonable
in these limited facilities to adopt a “scope‑first” paradigm:
patients are offered an upfront endoscopic approach with
the understanding that a shunt may ultimately be deemed
most appropriate. In such cases, parents are counseled
accordingly, and patients are positioned and prepped in
the operative suite for a possible VP shunt insertion. A low
threshold is maintained for aborting the ETV procedure when
intraoperative findings warrant: an opaque third ventricle
floor, heavy prepontine cistern scarring, or nonvisualization
of the basilar artery.
Equipment needs and surgical technique
In the illustrative cases that follow, ETV+CPC was performed
at the Philippine General Hospital using a Karl Storz flexible
neuroendoscope, following the technique described by
Warf.[11] The endoscope is held in place using a scope holder
that attaches to the bed frame [See Figure 1]. Under general
anesthesia, the patient is positioned supine with the head
slightly elevated and turned 90° to the contralateral side. The
head, neck, and abdomen are prepped and draped in case the
procedure needs to be converted to shunting. A semilunar
incision is made over the lateral portion of the anterior fontanel,
corresponding to Kocher’s point. The dural opening is kept to
a minimum, and after coagulation of pia, the lateral ventricle is
cannulated using a blunt trocar or 8 French feeding tube. CSF
is obtained for analysis, and the neuroendoscope is introduced
through this newly created tract. The ventricular anatomy is
inspected before navigating to the floor of the third ventricle.
a b
Figure 1: The typical setup for ETV+CPC using a flexible neuroendoscope is
shown in (a). The surgeon uses the right hand to navigate the endoscope within
the ventricles, while the left hand controls the lever which flexes the endoscope tip,
and the bugbee wire which is inserted in the working channel. In (b), the bugbee
wire is at the four o’clock position. The change in color observed after successful
cauterization of choroid plexus (CP) is demonstrated
S516 Neurology India | Volume 69 | Supplement 2 | November-December 2021
ETV is performed first. The stoma is created using the tip of the
bugbee wire without cautery. It is then enlarged using a Fogarty
balloon, or with experience, gentle traction in different directions,
avoiding the surrounding neurovascular structures. In most
cases, it is possible to insert the flexible scope through the stoma
into the prepontine cistern. The aim is to completely perforate
the Liliequist membrane, visualize the naked basilar artery, and
clear any redundant arachnoid tissue. At this point, the decision
is made whether to proceed to CPC or not. In patients ≥ 1‑year
old, ETV alone may be sufficient. In patients with cisterns
that are extensively scarred, particularly in postinfectious or
posthemorrhagic hydrocephalus, it is preferable to leave a shunt.
To perform CPC, the neurosurgeon must let the tip of the
bugbee wire glide on the surface of the choroid plexus, to and
fro, applying monopolar diathermy until the vessels change
in color from red/yellow‑orange to pale yellow. CPC is
accomplished in a logical manner: beginning at the foramen of
Monro, tracing the choroid plexus to the atrium, coagulating the
glomus, and finally, navigating to the temporal horn. The tip of
the monopolar electrode must not be buried within the choroid
plexus, and careful attention is given to the surrounding veins
and ependyma. If necessary, a septostomy is created. CPC is
then performed on the contralateral side following the same
sequence. Whenever possible, the neurosurgeon should aim for
bilateral complete CPC. Cauterizing >90% of choroid plexus in
the lateral ventricles has been associated with a greater chance
of treatment success.[13,14]
After CPC, the ETV is inspected to ensure patency and clear
any blood clot or debris. The endoscope is gently withdrawn,
checking for bleeding along its tract. Watertight dural closure
and meticulous apposition of galea and skin are essential to
reduce the risk of CSF leak and subsequent infection.
Rigid endoscopes, with their better optics and greater
familiarity to the operator, have also been used to accomplish
ETV+CPC.[23] However, flexible endoscopes have the advantage
of being able to maneuver to the temporal horns even when
ventricles are only moderately enlarged.[32] There is a learning
curve with the flexible endoscope, although it is less steep
with prior experience in rigid neuroendoscopy. Formal
training  (i.e.,  working alongside CCHU neurosurgeons) has
been associated with greater extent of CPC.[14]
Complications and postoperative care
A 2016 review of 11 studies with 524 patients showed that
adverse events after ETV+CPC occurred in 3.7%, with a
mortality rate of 0.4%.[33] Complications included hemorrhage,
CSF leak, meningitis, ventriculitis, SIADH, subdural hygroma,
and seizures. Perhaps the most dreaded intraoperative
complication is bleeding, but this is usually controlled with
irrigation. If needed, gentle tamponade may be applied
using the endoscope tip or an inflated Fogarty balloon. In the
event of major hemorrhage, the procedure is aborted, and an
external ventricular drain left in place. Head elevation and
intermittent irrigation using lactated Ringers help reduce the
occurrence of pneumocephalus, overdrainage, and massive
subdural collections. Because of the absence of hardware, the
risk of infection following ETV is low (~2%).[34,35] Prophylactic
antibiotics are given during induction following institutional
protocols, and layered closure is paramount.
 Baticulon and Dewan: ETV and CPC in infants
Vomiting and fever are not uncommon during the first 72 h, and
these are managed medically. Because of the approximately
5% risk of postoperative seizures, some neurosurgeons have
advocated for prophylactic antiepileptics.[36] In the authors’
practices, prophylactic antiepileptics are not routinely
prescribed. Patients are usually sent home within 3  days
postop, unless they live far away, in which case they are kept
admitted for a bit longer to monitor for early complications.
Long‑term follow‑up
Compared with shunting, ETVs have a higher rate of early
failure.[37] Most ETVs fail within 3–6 months following surgery.
In Warf’s original ETV+CPC series, median time to failure was
1.4 months, and 75% occurred within 2 months.[11] Corollary
to this, an ETV that is still functioning at 6 months is likely to
remain patent beyond this period, while a shunt inserted at
the same time in an identical patient will continue to be at risk
for failure. Therefore, follow‑up is generally recommended
at 2 weeks to check for wound complications; subsequently,
at 6 weeks, 3 months, and 6 months to monitor for early ETV
failure; and then less frequently thereafter.
The frequency of surveillance imaging depends largely on the
setting. At Vanderbilt University Medical Center, fast‑sequence
MRI is obtained at 2  weeks, 6  weeks, 3  months, 6  months,
and 1‑year postop. In contrast, at the Philippine General
Hospital, where capacity for imaging is limited and CT is more
affordable and readily available than MRI, post‑op scans are
advised at 6 months, but may be reasonably delayed to 1 year
in patients who are otherwise clinically improved. Patients
with incomplete CPC, evidence of past infection, and cisternal
scarring need to be monitored closely because they are at a
higher risk of failure. These are reflected in CCHU’s modified
ETVSS[38] that has been used to reliably predict outcome after
ETV+CPC in Uganda.
When ETV failure is suspected, ultrasound may be requested
initially to assess the thickness of the cortical mantle and
size of the ventricles. It is known that ventriculomegaly may
persist following an ETV, and the presence of large ventricles
alone—in the absence of definite progression and signs of
raised intracranial pressure—does not necessarily equate to
ETV failure.[39] Dewan and colleagues recommend monitoring
three signs: bulging fontanel, rapid increase in head
circumference as plotted on normal curves, and progression
of ventriculomegaly using either frontal and occipital horn
ratio or Evan’s index.[40]
Failure occurs because of two reasons: stoma closure or inability
of ETV+CPC to restore equilibrium between CSF production
and absorption.[41] As such, many have advocated for repeat
neuroendoscopy when a patient presents with signs of ETV
failure. Intraoperatively, if the stoma is found to be closed
or occluded, it is reopened  (“redo/repeat ETV”), and any
underlying arachnoid scarring or membrane is dissected free.
On the contrary, a patent stoma suggests that the latter reason
is responsible for ETV failure, and in this scenario, a VP shunt
is inserted. ETVs that fail early  (i.e.,  <3  months after initial
surgery) are more likely to require shunt placement.[41] Of note,
among patients who eventually need a shunt following a failed
ETV+CPC, the endoscopic procedure does not seem to increase
the subsequent risk of shunt infection or malfunction.[42]
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S517
To this day, questions on the long‑term durability of ETV+CPC
and its effect on neurocognitive development of children
with hydrocephalus have lingered, and this is the primary
reason for the cautious adoption of ETV+CPC elsewhere
around the world. A randomized trial of 100 Ugandan infants
with postinfectious hydrocephalus showed no significant
difference in cognitive outcome, using the Bayley Scales of
Infant Development at 12 months after either ETV+CPC or VP
shunting.[43] Patients who underwent endoscopic treatment had
larger ventricles on postop imaging, but median brain volume
was similar for both groups. This highlights the importance of
overall clinical assessment in the continuing care of children
after ETV+CPC.
Illustrative cases
Case 1: Congenital hydrocephalus
An 11‑month‑old boy presented with macrocephaly and a
bulging anterior fontanel [See Figure 2]. His pediatrician started
acetazolamide and requested for an MRI, which showed a
posterior fossa cyst, likely to be a Blake’s pouch cyst, associated
with supratentorial hydrocephalus. This relatively older infant
had noninfectious hydrocephalus, and thus, a favorable ETVSS
of 70. ETV+CPC was performed. On follow‑up, his head
circumference remained above average; however, the rate of
growth had decelerated, and the measurements plateaued
over time. The anterior fontanel remained flat and eventually
closed, despite discontinuation of diuretics. Consistent with
his clinical findings, repeat CT showed a decrease in the
size of the ventricles with an increase in the thickness of the
cerebral cortex. The child has remained well and on par with
developmental milestones.
Case 2: Idiopathic communicating hydrocephalus
A 6‑month‑old girl with no known history of perinatal
infection was referred for evaluation due to progressive
macrocephaly and preferential downward gaze (“sunset eyes”).
CT showed communicating hydrocephalus with no abnormal
enhancement [See Figure 3]. After discussion with the parents,
ETV+CPC was offered  (ETVSS: 40) and performed without
complications. Postop, there was an initial reduction in head
circumference. However, at 4 months post‑ETV, the increase in
head circumference began to accelerate once more, associated
with a bulging fontanel. Repeat CT revealed progression of
the ventriculomegaly. Redo endoscopy was contemplated, but
due to the etiology of the patient’s hydrocephalus, the decision
was made to proceed with VP shunting. As expected, the
head circumference stabilized, and surveillance scan showed
regression of the ventriculomegaly. Even with failure of
ETV+CPC, the treatment outcome remained favorable, and she
had no delay in her neurocognitive development, emphasizing
the importance of closely monitoring these patients.
Case 3: Shunt malfunction
A 6‑month‑old infant who previously underwent lumbar
myelomeningocele repair and shunt insertion presented with
frontal bossing and a bulging fontanel, consistent with shunt
malfunction [See Figure 4]. There were no signs of infection.
His CT showed favorable anatomy for a safe ETV; hence,
neuroendoscopy was performed (ETVSS: 50). After ETV, the
shunt was removed under direct visualization, cauterizing
the choroid plexus that had occluded the ventricular catheter
and averting intraventricular hemorrhage. Bilateral CPC
 Baticulon and Dewan: ETV and CPC in infants
a b c
Figure 2: Preoperative (a and b) and postoperative (c) images of patient in Case 1.
The planned trajectory for the ETV is illustrated with a dashed line in a. Treatment
success is evident with reduction in ventricular size and increase in cortical
thickness 8 months postop (FOHR: 0.56 to 0.48)
a b c worldwide. Childs Nerv Syst 2018;34:1837‑46.
Figure 3: Preoperative (a) and postoperative (b) images of patient in Case 2.
Four months after ETV+CPC for communicating hydrocephalus, the patient had
clinical signs of treatment failure, confirmed on CT (b) with an increase in FOHR
from 0.67 to 0.72. A ventriculoperitoneal shunt was inserted, with reduction in
ventriculomegaly and increase in brain volume seen after 1 year (c)
a b c 2007;107(Suppl 5):358‑64.
Figure 4: Preoperative images of patient in Case 3 showing a bulging anterior
fontanel and the tip of the proximal catheter (a), and adequacy of the prepontine
space (b). Choroid plexus (white arrow, c) that had occluded the proximal catheter
was cauterized before the shunt was removed. ETV and bilateral CPC were
successfully completed
was accomplished. The signs of raised intracranial pressure
resolved and the patient remained shunt‑free on last follow‑up.
This illustrates that previously shunted patients, especially
those with myelomeningocele and aqueductal stenosis should
be evaluated if they can be candidates for ETV+CPC when
they are readmitted for shunt failure, considering the positive
outcomes this subgroup of children can realize.
Conclusions
In appropriately selected infants, combined ETV+CPC is an
effective and safe treatment for hydrocephalus. A successful
outcome is seen in approximately 50–70% of patients in most
series, with greater likelihood of shunt freedom among infants
older than 1 month, those with noninfectious etiology such as
aqueductal stenosis and myelomeningocele, and those without
prior shunting. ETV failure usually occurs within 3–6 months,
particularly when CPC is incomplete, cisterns are scarred, and
hydrocephalus is postinfectious in origin. Studies on long‑term
functional and developmental outcomes will guide clinicians
in future decision making.
S518 Neurology India | Volume 69 | Supplement 2 | November-December 2021
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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 Original Article

Access this article online

Quick Response Code:
Complications Encountered with ETV in
Infants with Congenital Hydrocephalus
Rajat Verma, Chhitij Srivastava, Bal Krishna Ojha, Anil Chandra, R K Garg1,
Monica Kohli2, Hardeep Singh Malhotra1, Anit Parihar3, Shalini Tripathi4

Website:
www.neurologyindia.com
Abstract:
DOI: Background: Hydrocephalus is an abnormal excessive accumulation of cerebrospinal fluid  (CSF) in the
10.4103/0028-3886.332252 cavity and spaces of the brain. Endoscopic third ventriculostomy (ETV) has been an established treatment
modality for congenital hydrocephalus. However, in very young infants, the results are challenging. In our
study, we have evaluated whether ETV really offers an acceptable complication‑free postoperative course.
Objective: To study the complication and mortality rate in infants having congenital hydrocephalus treated
with ETV.
Materials and Methods: This is a single‑center prospective study conducted at the Department of
Neurosurgery, K. G. M. U, Lucknow, from January 2019 to February 2020. We studied 40 infants presenting
with clinical and radiological features suggestive of congenital hydrocephalus. Follow‑up was done at the first,
third, and sixth months after discharge.
Results: Nineteen infants (47.5%) required a second CSF diversion procedure at 6 months of follow‑up. The
failure rate was significantly higher in infants less than 3 months of age (P value of 0.04). The ETV site bulge
was the most frequent complication encountered in the postoperative period, occurring in 20% of the cases.
Eventually, all these infants required a ventriculoperitoneal shunt; 15% developed clinical features consistent
with the diagnosis of post‑ETV meningitis. The ETV site CSF leak occurred in 10% of the patients. Subdural
hygroma developed in 7.5% of the patients; 17.5% of the patients contributed to mortality with a mean time
of expiry of 22 days post‑procedure. All these deaths had multifactorial causes and could not be said as a
complication or failure of ETV.
Conclusion: We do not recommend ETV for infants less than 3 months because of a high failure rate. The
ETV site bulge was the most reliable and earliest marker of failure and a second CSF diversion surgery should
be immediately considered.
Key Words:
Complications, congenital, ETV, hydrocephalus, infants

Key Message:
Established superiority of ETV in providing a better complication profile compared to other methods of CSF
diversion in adults has not been reflected in the literature for infants yet. We have performed an adverse
event analysis of over 40 infants undergoing ETV.

Departments of H ydrocephalus is characterized by excessive

accumulation of the cerebrospinal fluid in
the cavity and spaces of the brain. The probable
high‑pressure ventricular cavity to low‑pressure
peritoneal/pleural or atrial cavity. Shunts carry
with them all the complications of installing a
Neurosurgery,
1
Neurology, causes can be congenital, infection, hemorrhage, foreign body inside the human body mostly for a
2
Anaesthiology, tumor, or infarct. Congenital etiology can be lifetime. Neuroendoscopy is another option with
3
Radiodiagnosis and correlated either with a defect in the development a preference for being more physiological. ETV
4
Pediatrics, Kings of CSF pathways or cerebral malformations makes a low‑resistance direct pathway for CSF
George Medical causing CSF to accumulate. The common to pass from the third ventricle to CSF cisterns.
University, Lucknow, causes are aqueductal stenosis, Dandy‑Walker But the question is whether ETV really offers a
Uttar Pradesh, India Malformation (DWM), and holoprosencephaly. better complication‑free postoperative course
CSF diversion is the main treatment of congenital and whether the morbidity and mortality are
Address for hydrocephalus. CSF diversion can be achieved lower than that associated with the shunt. This
correspondence: using shunts which drain CSF directly from
Dr. Rajat Verma, How to cite this article: Verma R, Srivastava C, Ojha BK,
397, Abhishek, This is an open access journal, and articles are distributed under the terms Chandra A, Garg RK, Kohli M, et al. Complications
Eldeco, Udyan 1, of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 Encountered with ETV in Infants with Congenital
Lucknow ‑ 226 002, License, which allows others to remix, tweak, and build upon the work Hydrocephalus. Neurol India 2021;69:S520-5.
Uttar Pradesh, India. non‑commercially, as long as appropriate credit is given and the new
creations are licensed under the identical terms. Submitted: 20‑May‑2021 Revised: 15‑Sep‑2021
E‑mail: vermarajat107@ Accepted: 07‑Oct‑2021 Published: 11-Dec-2021
gmail.com For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com

S520 © 2021 Neurology India, Neurological Society of India | Published by Wolters Kluwer - Medknow
 Verma, et al.: ETV In infants- a safe option?

question has been well answered in the literature but most of
the data pertain to the adult population. There are very few
studies which have considered infants as their study population
to evaluate ETV‑associated complications.
Aim
We aimed to perform an adverse event analysis over the
infants undergoing ETV for congenital hydrocephalus in our
institution during the study period.
Materials and Methods
This was a single‑center prospective study conducted at the
Department of Neurosurgery, K. G. M. U, Lucknow, from
January 2019 to February 2020. Forty infants presenting with an
increase in the head size or fullness of anterior fontanelle (AF)
with corroborative radiological features suggestive of
congenital hydrocephalus and mandating ETV were included
in the study. ETV was done using LOTTA endoscope has no full
form. Company- Karl Storz (LOTTA) 6‑degree ventriculoscope
system with a 6.1 mm diameter. It has one 2.9 mm working
channel and two 1.6 mm suction/irrigation ports with the
advantage of bimanual dissection. At the time of making a
burr hole on the table, before inserting the endoscope, an
External Ventricular Drain (EVD) was placed and the opening
pressure was recorded. At the end of the procedure, an EVD
was placed through the same burr hole in the ventricle to
monitor the intracranial pressure (ICP) in the postoperative
period for the first 3 days after the procedure. In every case,
the size of the stoma in the floor of the third ventricle was
enlarged to 8 mm with the help of a Fogarty catheter to ensure
its patency. Follow‑up was done at the first, third, and sixth
months after discharge with clinical features and a low‑dose
infant protocol computed tomography (CT) scan. The CT scan
was performed at the follow‑up and in the event of raised ICP
or the re‑appearance of the symptoms. The patient attendants
not willing to participate in the study and lost to follow‑up
were already excluded from the study.
The study was approved by the ethics committee of the institute.
Written informed consent was taken from the parents/legal
guardian before including in the study population. Those not
giving consent were excluded.

Results

Of these 40 infants, 34  (85%) were males and 6  (15%)

Image 1: CT axial section showing ETV site bulge in one infant
were females. The mean age of the study population was
4.66  ±  2.83  months  (range 1–12  months); 42.5% of the
infants fell under the age of 3 months while 20% were above
6 months. The failure rate of ETV was much higher in infants
less than 3  months of age  (P value of 0.04), setting the age
limit of 3  months as a benchmark deciding factor which

Image 2: Pre ETV

Image 3: Post ETV subdural hygroma

Neurology India | Volume 69 | Supplement 2 | November-December 2021 S521

 Verma, et al.: ETV In infants- a safe option?
Image 4: Subduroperitoneal shunt in situ
Image 6: Post ETV subdural hygroma
could independently predict the success rate of ETV in our
series. An abnormal progressive increase in the head size
was present in all 40  cases and bulging AF in 95% of the
cases. Intraoperatively, CSF was clear in 65%, hemorrhagic in
20%, and xanthochromic in 15% of the cases. The foramen of
Monro was grossly enlarged (almost double the size of scope)
in 66.7%. Septum pellucidum was deficient in 82.5% of the
infants. The basilar artery was visualized via the transparent
floor of the third ventricle in 87.5% of the cases. Low‑flow
hemorrhage, well‑controlled by irrigation with warm saline
occurred in 27.5% of the cases. High‑flow hemorrhage requiring
the use of electrocautery occurred in only one case  (2.5%).
Postoperatively, a progressively increasing ICP trend with
a difference of more than 2 mm of Hg between the third and
first day positively correlated with ETV failure. The morbidity
associated with the procedure can be best described in the form
of complications encountered, the need for additional surgery,
and mortality.
Complications encountered
ETV site bulge
The frequency of individual complications encountered
has been depicted in Table 1. ETV site bulge was the most
frequent complication encountered in the postoperative period
occurring in 20%  (eight) of the cases. ETV site bulge along
with its communication with persistently enlarged ventricle in
one of these infant has been shown in Image 1. It was initially
managed with serial lumbar punctures, but unfortunately, all of
these patients required placement of ventriculoperitoneal (VP)
shunt eventually. This was one of the earliest and most reliable
markers of the postoperative period consistent with ETV failure
in our study.
Post‑ETV meningitis
About 15%  (six) of the patients developed clinical features
consistent with the diagnosis of post‑ETV meningitis (like fever,
neck rigidity, poor oral intake, and failure to thrive). The only
S522 Neurology India | Volume 69 | Supplement 2 | November-December 2021
Image 5: Resolution of subdural hygroma
Image 7: Resolution of subdural hygroma in follow up imaging spontaneously
CSF finding in the routine examination done in the post‑op
period which showed the presence of infection was low sugar
levels (<20), however, four out of these six patients had their
culture positive. Acinetobacter was found in two patients,
coagulase‑negative staphylococcus in one, and pseudomonas in
one. Out of these six patients, two were successfully managed
with antibiotics and were discharged in healthy condition.
They were asymptomatic throughout the follow‑up period
and did not require any further intervention. In three patients,
meningitis was controlled with antibiotics and they eventually
required VP shunt. One infant succumbed to death revealing
the fatal nature of this complication despite all best efforts.
ETV site CSF leak
ETV site CSF leak was the next most common complication
accounting for 10% (four) of the patients. This was successfully
managed conservatively with medications (acetazolamide) and
serial lumbar punctures in two patients. However, the rest of
the two patients required VP shunt eventually. One of these
patients developed meningitis due to a persistent leak which
was managed successfully with antibiotics. But later, that
patient developed post‑infectious hydrocephalus for which a
shunt was required. This reflects the fact that there is always
a possible risk of developing meningitis in patients being
conservatively managed for CSF leak.
Others
Subdural hygroma developed in the perioperative period in
three patients but it was benign and asymptomatic in two.
In one case, it became large and a low‑pressure subdural
peritoneal shunt was required for its successful treatment.
Images 2-5 demonstrate the development of subdural
hygroma after ETV and its resolution after placement of
subduroperitoneal shunt. The other two patients did not
require VP shunt and the subdural hygroma gradually resolved
in follow‑up imaging. Image 6 demonstrate development of
subdural hygroma in one of these infants post ETV and image
 Verma, et al.: ETV In infants- a safe option?

70.00% Table 1: Frequency of complications causing

62.50% morbidity related to the procedure
60.00% 1 MONTH Complication Number Percent
3 MONTH ETV site bulge 8 20%
50.00% 47.50% Post‑ETV meningitis 6 15%
6 MONTH
42.50% CSF leak 4 10%
40%
40.00% Subdural hygroma 3 7.5%
35% IVH 1 2.5%
30.00% Post‑ETV seizures 1 2.5%
22.50% Mortality 7 17.5%
20.00% 17.50%17.50%
15%
Table  2: Factors influencing perioperative mortality
10.00% Predisposing factors for expiry in the perioperative Number
period of infants
0.00% Prematurity/preterm delivery 2
SUCCESS FAILURE EXPIRY
Low birth weight 2
Figure 1: Bar diagram showing success, failure and expiry rates at 1, 3 and 6 History of complications in pregnancy 2
months follow up History of ICU stay 3
History of failure to thrive 3
7 shows its spontaneous resolution in follow up imaging. Poor Denver score 2
Intraventricular hemorrhage (IVH) and post‑ETV seizures Opening pressure >20 3
occurred in one case each. Poor respiratory effort in post‑op period/irregular respiration 2
Need for reintubation in ward/ventilator support 3
Need for additional surgery
Hemorrhagic rashes and generalized edema 2
At 1 month of follow‑up, nine infants had the requirement
of VP shunt, and it was successfully placed in seven infants.
The guardians of the remaining two infants refused second period, her respiratory pattern was irregular. She was
surgery. We considered these two infants as our clinical reintubated and kept on ventilatory support, however, she
failure. Hence, the failure rate at 1 month of follow‑up was succumbed to death on postoperative day (POD) 3. The second
22.5%. At 3 months of follow‑up, eight more infants required child was an 8‑month male born with full‑term normal vaginal
VP shunt increasing the failure rate to 42.5%. Two more delivery presented with complaints of an increase in head
infants underwent VP shunting increasing the failure rate at size Head Circumference (HC: 54 cm) and bulging AF. The CT
six months to 47.5%. Failure rate at 1,3 & 6 months have been scan revealed triventriculomegaly with an Evans ratio of 0.75.
compared in Figure 1. The time to failure (period between the Periventricular lucency (PVL) was present and the prepontine
first and second surgeries) ranged from a minimum of 10 days space was 3  mm. The child had a Denver score of 8/15 at
to a maximum of 162 days with a mean of 52.65 ± 43.03 days. presentation with grossly delayed developmental milestones.
The median came out to be 50 days. The two clinical failures ETV was done and the opening pressure was 24 mmHg. The
had persistent ETV site bulge, abnormal progressive increase child was shifted to ICU, however, due to poor respiratory
in head circumference, failure to thrive, loss of appetite, sunset effort where he was reintubated. Despite all the efforts, he was
sign, and progressive ventriculomegaly in repeat CT scan, unable to maintain saturation ending in respiratory failure and
but unfortunately, their parents refused to give consent for expired on POD 1 itself.
repeat surgery.
The third was a 9‑month female child born as a preterm
Mortality delivery by cesarean section at 35  weeks. History of (H/O)
Unfortunately, there were three mortalities within 1 week premature rupture of the membrane and anemia in the mother
of the procedure during the hospital stay itself. One was a was present. H/O low birth weight along with delayed cry was
2.5 months female born as an identical twin via cesarian section present. The child had premature lung syndrome and was kept
at 32 weeks gestation with a birth weight of 1500 g. Her mother in ICU for 10 days post‑birth. She presented with complaints
had a history of anemia, previous abortion, and premature of irritability, abnormal increase in the head size (HC: 49 cm)
rupture of membranes in her current pregnancy. History of with bulging AF, and failure to thrive. The CT done showed
death of identical twin 18 h after delivery was present. The panventriculomegaly with a posterior fossa cyst. PVL was
cause of death was bronchopulmonary dysplasia/hyaline lung present, prepontine space was 4 mm, and the cortical mantle
disease. This infant, however, survived after an Intensive Care thickness was less than 5 mm. ETV was done. The opening
Unit (ICU) stay of seven days. She came to the hospital with pressure was 22 mmHg. The mean ICP on POD 1, 2, and 3
a progressive increase in head size for 1.5 months, recurrent were 5.12, 3.87, and 3.23. The patient developed febrile rashes
vomiting, loss of appetite, and failure to thrive. The head in the postoperative period along with hypotension. Phenytoin
circumference at presentation was 43.5 cm, AF was tense, and was stopped in view of suspicion of drug intolerance. The
the sunset sign was present. She had delayed developmental fever was refractory to paracetamol. Despite maximal fluid
milestones confirmed by a Denver score of 8/16. The CT of the and ionotropic support, the child succumbed to refractory
head was suggestive of congenital aqueductal stenosis. ETV hypotension and expired on POD 5. There were multiple
was done under high‑risk consent. During the postoperative factors common among these three children which could
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S523
 Verma, et al.: ETV In infants- a safe option?

Table 3: Complications and complication rate in the individual study population

Author with year Success rate (%) Complications Complication rate (%)
Tewuerbati et al.,[2] 2015 36.4 9 (5 seizure; 3 infection; 1 subdural hemorrhage) 20.5
Zohdi et al.,[3] 2013 12.5 1 (CSF leak and cardiac failure) 12.5
El Beltagy et al.,[4] 2010 0 N/A N/A
Gallo et al.,[5] 2010 39.1 2 (1 postoperative seizure; 1 intraoperative forniceal injury) 8.7
Ogiwara et al.,[6] 2010 34.8 3 (1 IVH; 1 meningitis 1 CSF leak) 13
Lipina et al.,[7] 2008 57.1 1 (subdural hygroma) 7.1
Baldauf et al.,[8] 2007 37.5 N/A N/A
Yadav et al.,[9] 2006 83.3 13 (4 bleeding/CSF leak/infection; 8 stoma blockage; 1 24.1
diabetes insipidus)
Koch‑Wiewrodt D et al.,[10] 2006 46.4% N/A N/A
Fritsch et al.,[11] 2005 75 N/A N/A
Warf et al.,[12] 2005 59.4 N/A N/A
Gorayeb et al.,[13] 2004 63.9 4 (not specified) 11.1
Koch and Wagner,[14] 2004 31.3 3 (2 CSF leakage; 1 minor intraoperative venous bleed) 18.8
Javadpour et al.,[15] 2001 33.3 2 (CSF leak, transient hyponatremia) 9.5
Kim et al.,[16] 2000 33.3 2 (oculomotor nerve palsy) 33.3
Murshid et al.,[17] 2000 69.2 8 (SDH, DI, wound infection, pyrexia, IVH, oculomotor and 61.5
abducens nerve palsies)
Hopf et al.,[18] 1999 100 Death at 3 and 7 months (Due to underlying pathology) 0
Goumnerova et al.,[19] 1997 33.3 0 0
Kunz et al.,[20] 1994 0 0 0
Teo and Jones,[21] 1996 25 2 (minor scalp abscess and subdural hematoma) 40
Our study 35 ETV site bulge 8, CSF leak 6, meningitis 4, subdural 37.5
hygroma 3, IVH 1, seizures 1

Table 4: Complications and complication rate in a The median value was 17 days (again in the 3rd week). Unlike
combined study population of comparative studies the perioperative deaths (3/7), which occurred in the hospital
Complication Complication Complication Complication stay itself, the follow‑up mortalities were at the home of the
rate rate patient. A detailed interrogation from the parents revealed that
Postoperative 10; 25% Subdural 3; 7.5% the children were well for a few days after discharge but the
pyrexia hematoma symptoms reappeared after varying periods and progressed
CSF leak 6; 15% Wound infection 3; 7.5% rapidly resulting in their deaths before they could even contact
Meningitis 4;10% Oculomotor nerve 3; 7.5% a medical facility. Thus, as per their statements, the cause of
palsy death appeared neurological contrary to perioperative deaths
Diabetes 2; 5% IVH 3; 7.5% in which the cause appeared to be poor tolerability of the
insipidus candidates for surgery. However, the follow‑up mortalities
Seizures 1; 2.5% Forniceal injury 1; 2.5% appeared to be from either failure of ETV to bring about
the clinical improvement or more likely the recurrence of
hydrocephalus causing sudden deterioration.
be an associated cause of mortality. They are compiled in
Table 2. There was no gross abnormality in the CT scan
done in the immediate postoperative period of these infants. Discussion
They had normal postoperative ICP trends and normal CSF
biochemical and microbiological reports which were retrieved Zaben et al.[1] compiled the data of 19 studies addressing
later. Prematurity, low birth weight, hyaline lung disease, pediatric congenital hydrocephalus and did a systematic
ICU stay, poor nutritional status, and ventilator dependency review and meta‑analysis. They studied a total of
were the factors responsible for making these three children 399 patients with a mean age of 4.2 months (range: 34 weeks
poor surgical candidates for ETV. There were three expiries at gestation to 12 months). The complication rates varied from
1-month follow-up period contributing 7.5% to the expiry rate. 7.1 to 61.5% among these studies. The complications in the
Thus, if we include perioperative deaths, overall, the expiry individual studies are compiled in Table 3. The frequency of
rate at a 1 month becomes 15%. The overall expiry rate at 3 individual complication in the combined study population
months was 17.5%. Fortunately, no deaths occurred between 3 has been depicted in Table 4. The demographic analysis
and 6 months of follow-up, hence, the expiry rate at 6 months of our study clearly established the supremacy of ETV in
remained the same as that of the 3 months (17.5%). Mortality infants older than 3 months. There was a deviation toward
rate at 1,3 & 6 months have been compared in Figure 1. the lower age group  (3  months) as compared to most of
the studies in the meta‑analysis  (6  months) because 80%
The time to expiry (period between ETV and expiry) ranged of our infants were younger than 6 months. This caused
from 1 day after operation to 66 days after the operation. The a bias in the population age distribution shifting all our
mean time to expiry was 21.71 days, that is, around 3 weeks. results, more reflective of a study population less than

S524 Neurology India | Volume 69 | Supplement 2 | November-December 2021

 Verma, et al.: ETV In infants- a safe option?
6 months old rather than 1 year. Almost 90% of ETV failure
and 100% of mortality occurred within 3  months of the
procedure. This emphasized the importance of frequent and
regular follow‑up of the cases for at least the first 3 months
post‑procedure. Another important implication which could
be drawn from our study was that the ETV site bulge requires
definitive correction with surgery, the lumbar punctures
do not work. Subdural hygroma, if it occurs, need not to
be intervened until it produces clinical symptoms of mass
effect or significant midline shift. It may indicate a defect
at the absorption level with a well‑functioning ETV stoma
which tends to improve with time in most cases. The three
mortalities which occurred within 1 week of the surgery
could be attributed to the general condition of the child as
neither there was any definite evidence of intraoperative
hypothalamic or brainstem injury nor any evidence of IVH
in the postoperative scans.
Conclusion
About 80% of our study population was less than six months
old. Most of the morbidity and mortality occurred within
three months of the surgery. The ETV site bulge was the most
reliable and earliest marker of failure. Meningitis, if occurs,
is a significant poor prognostic indicator. Symptomatic
subdural hygroma not resolving spontaneously can require
surgery. We do not recommend ETV for infants less than
3 months because of a high failure rate. In infants older than
3 months, it should be performed under aseptic conditions
to avoid meningitis—the single most fatal complication.
If the ETV site bulge occurs, it indicates stoma failure and
requires an alternative diversion strategy. A limited number
of patients and short follow‑up were the limitations of the
study.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References
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 Review Article
Access this article online
Quick Response Code:
Website:
www.neurologyindia.com
DOI:
10.4103/0028-3886.332268
Division of Paediatric
Neurosurgery, Department
of Neurosurgery, Amrita
Institute Of Medical Sciences
and Research Centre, Kochi,
Kerala, 1Department of
Neurosurgery, Narayana Institute
of Neurosciences, Bengaluru,
Karnataka, 2Department
of Neurosurgery, National
Institute of Mental Health and
Neurosciences, Bengaluru,
Karnataka, 3Department
of Neurosurgery, Nizam’s
Institute of Medical Sciences,
Hyderabad, Telangana,
Consultant Neurosurgeon,
4
Sunshine Hospitals,
Secunderabad, Telangana,
Institute of Neurosciences,
5 was used to provide recommendations for several issues.
AIG Hospitals, Hyderabad,
Telangana, 6Department
of Neurosurgery, All India
Institute of Medical Sciences,
New Delhi, 7Department of
Neurosurgery, Krishna Institute
of Medical Science, Hyderabad,
Telangana, 8Neurosciences,
Brains Hospitals, Bengaluru,
Karnataka, 9Department of
Neurological Sciences, Christian
Medical College Hospital, Vellore,
Tamil Nadu, 10Department of
Neurosurgery, Global Hospital,
Mumbai, Maharashtra, India
Address for
correspondence:
Prof. Suhas Udayakumaran,
Division of Paediatric
Neurosurgery, Department
of Neurosurgery,
Amrita Institute Of
Medical Sciences and
Research Centre, Kochi,
Kerala ‑ 682 041, India.
E‑mail: dr.suhas@gmail.
com
S526 © 2021 Neurology India, Neurological Society of India | Published by Wolters Kluwer - Medknow
Indian Society of Pediatric
Neurosurgery Consensus Guidelines
on Preventing and Managing Shunt
Infection: Version 2020‑21
Suhas Udayakumaran, Shibu Pillai1, Srinivas Dwarakanath2, Suchanda Bhattacharjee3,
Naveen Mehrotra4, Subodh Raju5, Deepak Gupta6, Manas Panigrahi7,
Neelam K Venkataramana8, Vedantam Rajshekhar9, Suresh Sankhla10
Abstract:
Background: Shunt infection is the most significant morbidity associated with shunt surgery. Based on
the existing literature for the prevention and management of shunt infection, region and resource‑specific
recommendations are needed.
Methods: In February 2020, a Guidelines Development Group (GDG) was created by the Indian Society of
Paediatric Neurosurgery (IndSPN) to formulate guidelines on shunt infections, which would be relevant to
our country and LMIC in general. An initial email survey identified existing practices among the membership
of the IndSPN, and eight broad issues pertaining to shunt infection were identified. Next, members of the
GDG performed a systematic review of the literature on the prevention and management of shunt infection.
Then, through a series of virtual meetings of the GDG over 1 year, evidence from the literature was presented
to all the members and consensus was built on different aspects of shunt infection. Finally, the guidelines
document was drafted and circulated among the GDG for final approval. Grading of Recommendations
Assessment, Development and Evaluation (GRADE) system was used to grade the evidence and strength
of recommendation.
Results: The guidelines are divided into eight sections. Level I and Level II evidence was available for only
five recommendations and led to a moderate level of recommendations. Most of the available evidence was
at Level III and below, and hence the level of recommendation was low or very low. A consensus method
Conclusions: Although most of the recommendations for the prevention and management of shunt infections
are based on a low level of evidence, we believe that this document will provide a useful reference to
neurosurgeons not only in India but also in other low and middle income countries. These guidelines need to
be updated as and when new evidence emerges.
Key Words:
Complications, consensus, hydrocephalus, systematic review, ventriculoperitoneal shunt
Key Message:
This guidelines document for shunt infection presents pragmatic, evidence‑based recommendations derived
from consensus among experts and evidence.
S hunt infection is the most significant morbidity
associated with shunt surgery. Currently, no
international guidelines are available for shunt
between evidence available in the literature and
the ground reality of resource constraints.
infections, and there is inconsistency in the The overarching intention of the committee
interpretation of evidence and recommendations was to create a document that would provide
in the existing literature.
It is a challenge to create guidelines for a developing How to cite this article: Udayakumaran S,
country. There needs to be a careful balance Pillai S, Dwarakanath S, Bhattacharjee S, Mehrotra N,
Raju S, et al. Indian Society of Pediatric Neurosurgery
This is an open access journal, and articles are distributed under the terms Consensus Guidelines on Preventing and Managing
of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 Shunt Infection: Version 2020-21. Neurol India
License, which allows others to remix, tweak, and build upon the work 2021;69:S526-55.
non‑commercially, as long as appropriate credit is given and the new
creations are licensed under the identical terms. Submitted: 08‑Jun‑2021 Revised: 16-Sep-2021
Accepted: 16-Sep-2021 Published: 11-Dec-2021
For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com
 Udayakumaran, et al.: IndSPN Shunt guidelines 2021
guidelines pertaining to shunt infection that achieves this
balance. However, we were also cognizant of the wide disparity
in the practice situations of neurosurgeons in our country and
factored this into our guidelines.
Methods
In February 2020, a Guidelines Development Group  (GDG)
consisting of 11 senior neurosurgeons was created by the
Indian Society of Paediatric Neurosurgery  (IndSPN) to build
the guidelines on shunt infections, which would apply to our
country and low and middle income countries (LMIC) in general.
The guidelines development process involved the following
steps:
1. Identification of relevant questions, primary critical
outcomes and priority topics and formulation of a series of
questions structured in a PICO (Population, Intervention,
Comparison, Outcomes) format.
2. Document prevalent practices concerning the fundamental
issues pertaining to shunt infection through an email
survey among Indian neurosurgeons. The first author (S.U)
constructed the questionnaire, which was refined after
circulating it among 15 senior neurosurgeons.
3. Based on the responses to the survey, seven broad questions
on the issue of shunt infection were formulated.
A systematic review of the literature, using a standardized
methodology, was performed to retrieve evidence from
the Cochrane database of systematic reviews, MEDLINE,
Embase, Web of Science, and PubMed until June 30, 2021.
Additionally, we also reviewed reference lists of the
retrieved publications and review articles.
4. For queries that did not have significant evidence available
in the literature, a consensus opinion was created among
the GDG.
5. Evidence from the literature for each of the seven broad
questions was presented and discussed through a series
of six virtual consultations by the GDG. At the end of each
such consultation consensus guidelines for each broad
question were arrived upon.
6. The recommendations were assigned a level of evidence
and strength of recommendation, based on the Grading
of Recommendations Assessment, Development and
Evaluation (GRADE) system of grading.[1‑4]
7. The composite guidelines were ratified in a final online
meeting.
8. Finally, the guidelines draft document was circulated
among the GDG for final modifications and approval.
The Architecture of the Statement
The guidelines document is divided into eight sections.
Each section deals with a different issue pertaining to shunt
infection.
These guidelines aim to provide a comprehensive range of
evidence‑based recommendations for interventions to be
applied to avoid shunt infection during the pre‑, intra‑ and
postoperative periods. Additionally, it also proposes
recommendations for the management of active infection.
The guidelines have factored in the best available evidence
and the resources likely to be available in different practice
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S527
settings in our country. The guidelines are intended for
patients undergoing shunt of all ages, although some
recommendations may be specific for the pediatric population.
Each statement is followed by the closest level of evidence and
strength of recommendation following the GRADE system
of nomenclature.[4] Selected references directly pertaining to
the recommendation are included in the guideline document,
whereas a detailed literature review with a complete
bibliography is available in the online supplementary material.
Aim
To create national guidelines for avoiding and managing shunt
infections, which are practical and can be applied in most
practice settings in our country.
Results and Discussion
Global guidelines for preventing surgical site infection (SSI)
were published on November 3, 2016 by the World Health
Organization, then updated in some parts, and published in a
new edition in December 2016.[5,6]
In the current guidelines, we do not discuss the general aspects of
preventing SSIs or asepsis in the operating room and sterilization.
They were not the objects of formal recommendations.
The recommendations are followed by the level of evidence
and strength of recommendation following the GRADE system
in brackets at the end of the statement or statements (if it holds
good for all statements) [Table 1].
Section I
Perioperative Avoidance Of Shunt Infection
1.1 Preoperative
A.General considerations
Patient factors and avoidance of shunt infection
1.1.1 CSF PARAMETERS (Excluding postshunt infection)
RECOMMENDATIONS:
i. There is insufficient evidence to recommend a specific CSF
parameter to direct the timing of shunt placement in any
age group. (III, VERY LOW)
ii. There is insufficient evidence to recommend a particular
infant age and weight to direct shunt placement timing.
Placement of the shunt should be timed when the ‘infant’s
age, weight, and overall stability would allow.[7] (III, VERY
LOW)
iii. There is no evidence to recommend any etiology‑specific
timing. (III, VERY LOW)
1.1.2 INFECTIVE FOCUS ELSEWHERE: IS IT A
CONTRAINDICATION FOR SHUNT?
RECOMMENDATION:
Systemic inflammatory response syndrome  (SIRS) is not an
absolute contraindication to placing a ventriculoperitoneal
shunt  (VPS). There is no evidence suggesting the direct
 Udayakumaran, et al.: IndSPN Shunt guidelines 2021
association of VPS infection with SIRS. If the clinical situation
permits, the shunt placement should be delayed until the
treatment of the identified infective focus is started and/or
completed.[8] (III, MODERATE)
1.1.3 ROLE OF PREOPERATIVE NUTRITION
RECOMMENDATION:
If the shunt is not urgent, preoperative administration
of oral or enteral multiple nutrient‑enhanced nutritional
formulas is suggested in underweight patients.[9] (III, VERY
LOW)
1 . 1 . 4  S H U N T S U R G E R Y IN PATIENTS ON
IMMUNOSUPPRESSANT DRUGS
RECOMMENDATIONS:
i. It is recommended not to suspend or withdraw systemic
immunosuppressive therapy before shunt surgery to
reduce infection.[9,10] (III, VERY LOW)
ii. Extended antibiotic prophylaxis is not recommended in
these patients.[10] (III, VERY LOW)
1.1.5 MRSA SURVEILLANCE/SCREENING
RECOMMENDATIONS
i. Systematic screening and decolonization of Staphylococcu.
aureus carrier before surgery is not recommended.[5,9,11,12] (III,
VERY LOW)
ii. It is recommended that patients who are known nasal
carriers of Staphylococcus aureus undergoing shunt surgery
should receive perioperative intranasal applications of
mupirocin 2% ointment with or without a combination of
chlorhexidine gluconate body wash.[11] (IV, MODERATE)
1.1.6  SURGEON’S EXPERIENCE IN PEDIATRIC NEUROSURGERY
RECOMMENDATION
Shunt surgery in the high‑risk age groups such as premature,
infants, and younger children and revision surgeries
should be performed by an experienced surgeon/pediatric
neurosurgeon or under the supervision of such surgeons if
logistics permit or be performed in a high‑volume center.[13‑15]
(III, MODERATE)
PERIOPERATIVE (Table 2: Recommendations 1.1.1,‑8,‑10,‑1
1,‑‑12,‑13,‑14,‑16)[5,9,16‑25]
1.1.7 ROLE OF PROTOCOL‑GUIDED MANAGEMENT (Table 2,
Fig. 1 IndSPN Shunt Protocol)
RECOMMENDATION
The use and adherence to a standardized shunt surgery protocol
is recommended to reduce shunt infection rates.[23,24,26‑28]  (II,
MODERATE)
1.1.9 HEAD SHAVING
RECOMMENDATION
Clipping should be preferred over shaving if hair removal
is necessary; clipping per se may not reduce SSI. [29]  (III,
MODERATE)
S528 Neurology India | Volume 69 | Supplement 2 | November-December 2021
1.1.14 ANTIMICROBIAL COATED SUTURES
RECOMMENDATION
The use of antimicrobial sutures is strongly recommended.[30] (I,
STRONG)
1.1.18 USE OF TOPICAL ANTIBIOTICS
RECOMMENDATIONS
Topical antibiotics applied to surgical wound healing by
primary intention probably reduce SSI risk relative to no
antibiotic. There is no apparent difference in the efficacy of
different antibiotics used for topical application.[9]  (III/IV,
MODERATE)
Section 2
ANTIBIOTIC PROPHYLAXIS AND ROLE OF THE
ANTIBIOTIC‑IMPREGNATED SHUNT
2.1. ROLE OF PROPHYLACTIC ANTIBIOTICS FOR
PREVENTING SHUNT INFECTION
RECOMMENDATION
It is recommended to use perioperative antibiotics for
prophylaxis against shunt infection in patients with
hydrocephalus.[19,31‑33] (II, MODERATE)
2.2 CHOICE OF ANTIBIOTICS, APPROPRIATE DOSAGE, ROUTE,
AND DURATION OF PROPHYLACTIC ANTIBIOTICS
RECOMMENDATIONS:
i. Intravenous broad‑spectrum antibiotics with good
CSF penetration, covering the microorganisms
usually associated with shunt infections,
p re fe rab ly highe r ge ne ratio n c e p halospor in, is
recommended for prophylaxis against shunt
infection. [34,35] (II, MODERATE)
ii. Antibiotics for prophylaxis should be given at least
30–60  minutes  (120  minutes if vancomycin) before the
incision. Its use beyond 24 hours is not recommended,
even in specific situations that are considered at higher
risk for shunt infection, namely immunocompromised and
vulnerable groups such as premature infants.[9,19,33,36,37] (II,
MODERATE) [Figure 1]
iii. Use of vancomycin, second‑generation cephalosporins,
or any other antibiotics in isolation or combination
should be based on hospital antibiogram with due
consideration to the pharmacological properties and
adjusted to the type of patient  (body mass index,
renal or hepatic function, and variables that could
affect the distribution of the antibiotic). [36,37]   (II,
MODERATE)
iv. Evidence was uncertain for intrathecal administration of
antibiotics for prophylaxis.[36‑38] (III, LOW)
2.3 ROLE OF THE ANTIBIOTIC‑IMPREGNATED SHUNT
IN AVOIDING SHUNT INFECTIONS
RECOMMENDATION
i. The use of an antibiotic‑impregnated shunt implant
is desirable. It may offer extended protection against
infections due to gram positive organisms but may not
provide any advantage against gram negative infections
 Udayakumaran, et al.: IndSPN Shunt guidelines 2021
Figure 1: IndSPN Shunt Protocol
and other atypical microorganisms.[39,40] (I, HIGH)
ii. Antibiotic‑impregnated shunt implant may be preferable
in specific situations, such as premature infants, neonates,
immunocompromised patients, and replacement of infected
shunts.[41] (III, MODERATE)
Section III
DIAGNOSIS OF SHUNT INFECTIONS
3.1 ESSENTIAL CRITERIA FOR DIAGNOSIS OF SHUNT
INFECTION[23,42]
RECOMMENDATIONS
Any one of the following:
i. Identification of organisms on culture or gram stain in the
CSF or from a wound swab (if the pathogen is interpreted
as relevant), or pseudocyst fluid.
ii. CSF pleocytosis associated with fever (body temperature
38° Celsius), neurological symptoms, abdominal signs or
symptoms, or shunt malfunction.
iii. Abdominal pseudocyst  (even in the absence of positive
cultures).
iv. Positive blood cultures in a child with a ventriculoatrial
shunt (VA).
v. Shunt erosion (defined as wound breakdown with visible
shunt hardware). (III, IV, MODERATE)
3.2 DIAGNOSIS OF SHUNT INFECTION
RECOMMENDATIONS
The following samples should be sent for diagnosis of shunt
infection:
i. The CSF samples obtained from shunt tap or at the time of
catheter externalization (highest yield), ventricular tap, or
lumbar puncture should be sent for aerobic and anaerobic
culture in a sterile test tube. Routine microbiological CSF
observation should extend for 10 days.[43,44]
ii. The distal catheter tip should be sent in a sterile manner
for culture, wherever the shunt is externalized.[43]
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S529
iii. Blood cultures and urine routine should be sent in patients
with VA shunts.[23]
iv. Pseudocyst fluid should be sent for culture.[42,45]
v. A wound swab is mandatory in case of wound infection.[23]
(III/IV, MODERATE)
Other ancillary investigations recommended, which may be
nonspecific but can corroborate the diagnosis of shunt infection,
include white blood cell counts, blood and/or CSF CRP and
procalcitonin and neuroimaging (addressed explicitly in the
following section).[42,46] (III/IV, MODERATE)
3.3 RECOMMENDATIONS FOR IMAGING IN SHUNT
INFECTIONS
RECOMMENDATIONS
i. Neuroimaging is recommended in all patients suspected
to have shunt infection.[47,48]
ii. Contrast‑enhanced computed tomography  (CT) or
preferably magnetic resonance imaging (MRI) should be
an essential part of evaluating the management of shunt
infection.[49,50] Neurosonogram can be an option in neonates
and infants with open fontanelle.
iii. If abdominal symptoms or signs (e.g., pain, peritonitis, or
tenderness) or pseudocyst abdomen is suspected, CT or
ultrasound (US) of the abdomen should be done.
iv. Echocardiography should be done when a VA shunt
infection is suspected.
(IV/V, LOW)
3.4 CULTURE‑NEGATIVE CSF BUT HIGHLY SUSPICIOUS
CLINICAL/LABORATORY PICTURE OF INFECTION
RECOMMENDATIONS
If CSF culture is negative, the following steps are recommended
in an attempt to confirm shunt infection:
i. Review clinical symptoms, signs, overall clinical scenario
including proximity to the shunt surgery/index exposure.
 Udayakumaran, et al.: IndSPN Shunt guidelines 2021

ii. Review ancillary laboratory tests. third‑generation cephalosporin with gram positive cover
iii. Repeat CSF culture, maintaining the culture for observation is recommended.[52]
for at least 10 days. (Table 1, Annexure II, Supplementary material online)
iv. C S F P C R a n d g a l a c t o m a n n a n   ( e s p e c i a l l y i n ii. Meropenem and/or any higher antibiotics should be
immunocompromised) if clinically relevant.[51]  (IV/V, reserved for empiric therapy when hospital‑acquired
LOW) infections by extended‑spectrum beta‑lactamase‑producing
gram‑negative bacilli  (ESBL‑GNB and Acinetobacter
Section IV baumannii) are thought to be highly probable.[52]
MANAGEMENT OF SHUNT INFECTION‑ DRUG iii. Empiric therapy should also include antibiotics that have
THERAPY been identified as effective during the management of
previous shunt infections or concurrent infections occurring
4.1 ANTIBIOTIC PROTOCOL FOR BACTERIAL SHUNT
elsewhere in the body.[52] (IV/V, LOW)
INFECTION
iv. Antibiotic treatment should be supplemented by
4.1.1 EMPIRICAL ANTIBIOTICS FOR BACTERIAL SHUNT
INFECTION
externalization or with complete shunt hardware
removal (II, Moderate)
RECOMMENDATIONS:
Annexure‑II, Supplementary material online, TABLE 1:
Empiric Therapy‑ Primary and alternative drugs with a
i. Empiric therapy for shunt infection should be based
total daily dose.
on pathogens that have been commonly isolated in
patients with shunt infection in that practice setting 4.1.2 DEFINITIVE ANTIBIOTICS IN A PROVEN BACTERIAL
and their sensitivity; however, in general intravenous, a SHUNT INFECTION
RECOMMENDATIONS:
Table 1: Content map
CONTENTS i. Once the organism causing the infection has been identified,
Section I Perioperative avoidance of shunt infection the treatment should be based on the intravenous use
Section II Antibiotic prophylaxis and role of the
of sensitive antibiotics and their minimum inhibitory
antibiotic-impregnated shunt concentration (MIC).
Section III Diagnosis of shunt infections
ii. The addition of rifampicin is recommended in retained
infected shunt hardware.[53‑55]
Section IV Management of shunt infection- drug therapy
iii. In resistant gram‑negative organisms, prolonged
Section V Role of other drugs in shunt infection
intravenous infusion of meropenem with each dose
Section VI Surgical management of shunt infection
administered over  3 hours or continuous intravenous
Section VII Special situations associated with shunt infusion may help treat the infection.[56‑58]
Section VIII Management differences in va shunt iv. C o m b i n e d i n t r a v e n o u s a n d i n t r a v e n t r i c u l a r

Table 2: Perioperative recommendations to avoid shunt infections

Recommendation Issue Recommendation Level of Strength of Comments
Number evidence recommendation
1.1.1 Etiology‑specific No specific III Very low
timing recommendation
1.1.8 Preoperative hair Patients should take III Low Patients should be provided detailed
washing with a shower on the day information about the steps to follow for
chlorhexidine? of the procedure with utmost efficacy[19]
chlorhexidine soap[5,9,23,24]
1.1.10 Surgical duration[16‑18] Should be a part of the IV Low Duration <30 min
shunt protocol bundle
1.1.11 Theatre discipline[16] Not supported by evidence III Low ‑First surgery in the morning
to recommend. However, ‑Sign outside the door minimizing traffic
it should be a part of the ‑Senior experienced staff
protocol bundle.
‑Limited implant
minimal personnel in the operating room
1.1.12 Double gloving[21,22] It should be a part of the III Low To avoid the risk of accidental tear and
protocol bundle. occasional inherent perforations
1.1.13 Intraoperative glove Intraoperative glove Minimal handling of implant “”no‑touch
change[25] change is recommended technique””.
1.1.14 Wound irrigation with Immersing shunt in IV Low No evidence for this practice.
antibiotics, immersing antibiotic solutions cannot Wound irrigation is suggested at the end
the shunt in antibiotic be recommended because of the procedure with a moderate amount
solution/bacitracin. of a lack of evidence of a pressurised solution to remove
detritus and foreign bodies.[19]
1.1.16 Meticulous Surgical (III/IV) Low Limited skin manipulation
principles[16] Avoiding CSF leak[20]

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 Udayakumaran, et al.: IndSPN Shunt guidelines 2021
colistin  (colistemethate sodium) or polymyxin B is
recommended for multidrug‑resistant Acinetobacter
species.[56‑58] (IV/V, LOW)
Supplementary material online, Annexure‑II, TABLE 2.
Definitive Therapy‑  Primary drugs and alternative drugs
with a total daily dose
4.2  ANTIBIOTICS FOR FUNGAL SHUNT INFECTION
RECOMMENDATIONS
Treatment for fungal shunt infection depends on the causative
organism.
The dosage used for various microorganisms is mentioned in
TABLE 3 (Supplementary material online, Annexure‑II).
i. Candida ventriculitis is treated with liposomal amphotericin
B, which achieves higher CSF concentrations than other
preparations, with or without oral flucytosine. Following
the clinical response, treatment can be stepped down to
fluconazole. Antibiotics need to be continued till all signs,
symptoms, CSF, and radiological abnormalities have
resolved.[59‑61] (IV/, V, VERY LOW)
ii. The recommended treatment for aspergillus ventriculitis and
meningitis is voriconazole. Antiseizure medications such as
phenytoin and phenobarbitone, which can reduce the serum
levels of voriconazole to subtherapeutic levels, may need
to be avoided. Posaconazole and liposomal amphotericin
B are alternatives if the patient is intolerant or refractory
to voriconazole. The antifungals are continued for several
months or till the patient is no longer immunosuppressed
and has recovered clinically.[62,63] (IV/, V, VERY LOW)
4.3  INTRAVENTRICULAR OR INTRATHECAL ANTIBIOTICS
4.3.1 RECOMMENDATIONS
i. Intraventricular (IVT) or intrathecal (ITC) therapy should
be added to intravenous antibiotics (but should not be used
as the only therapy) in the following situations:
a. When the infection is unresponsive to intravenous
therapy alone.
b. When shunt infection is due to MDR gram‑negative
organisms, especially acinetobacter.
c. In the presence of retained hardware such as the whole
shunt or an externalized shunt.[56‑58,64,65]
ii. There is insufficient evidence to recommend using IT/
IVT with/without intravenous antibiotics in the setting of
pediatric shunt infection and neonates.[66‑68]
(IV/V, VERY LOW)
4.3.2 WHAT ARE THE DRUGS THAT CAN BE USED FOR IVT/ITC
THERAPY AND THEIR DOSAGE?
The doses are empiric recommendations without specific data
to back them.[46,69]
Supplementary material online, Annexure‑II, TABLE  4: The
recommended dosage of Antimicrobials for Intraventricular
and intrathecal use. (IV/V, VERY LOW)
4.3.3 WHAT IS THE OPTIMAL DURATION OF ANTIMICROBIAL
TREATMENT FOR SHUNT INFECTION?
RECOMMENDATIONS
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S531
i. Continue intravenous antibiotics for 10–14 days when CSF
cultures are negative from the start of therapy or when
CSF cultures rapidly (by 48–72 hours) turn negative after
treatment.[70,71]
ii. When the CSF cultures are repeatedly positive while
on appropriate antimicrobial therapy, treatment
should be continued 10–14  days after the last negative
culture.[70,71] Prolonging beyond this period may not have
any advantage.[72]
iii. Fungal shunt infections will need to be treated till all
symptoms, signs, CSF, and radiological markers are normal.
Sometimes, especially in immunosuppressed individuals,
this may need to be continued for several months till the
patient is no longer immunosuppressed and is clinically
well.[59‑61] (IV/V, VERY LOW)
Section V
ROLE OF OTHER DRUGS IN SHUNT INFECTION
5.1  ROLE OF STEROIDS
RECOMMENDATION
Steroids have no role in the treatment of shunt infections
There are no studies evaluating the role of steroids in the
treatment of shunt infection (UNCERTAIN LEVEL)
5.2  ROLE OF ANTICONVULSANTS
RECOMMENDATIONS
i. Antiepileptic medication is essential in patients who
present with seizures due to shunt infection.[73,74] In all
other situations, in the absence of seizures, the indication
for anticonvulsants is not clear and hence cannot be
recommended. Furthermore, the surgeon’s judgement
in a particular clinical situation  (severe ventriculitis,
altered sensorium) has to be relied upon for decision
making.
ii. Levetiracetam is the preferred antiepileptic medication if
antiepileptics are being initiated. In a patient with shunt
infection who is already on antiepileptic drugs, these drugs
should be continued. A close watch should be kept to avoid
adverse interactions with antimicrobials to treat the shunt
infection.[73] (IV/V, VERY LOW)
Supplementary Material, Annexure‑II, Table  5. Drug
interactions between antiepileptics and antimicrobials
Section VI
SURGICAL MANAGEMENT OF SHUNT INFECTION
6.1 TEMPORIZING OPTIONS FOR MANAGING
HYDROCEPHALUS IN A SHUNT‑DEPENDENT INDIVIDUAL
WITH SHUNT INFECTION
RECOMMENDATIONS
i. There is insufficient evidence to recommend either complete
removal or externalization as the preferred treatment option
to manage CSF shunt infection.[55,66,72]
ii. Externalization may be done with a new implant, with
the less‑preferred option being to externalize the existing
implant.[55,72]
iii. Use of Ventriculosubgaleal shunt or a reservoir or fontanelle
tap may be options in infants and very young to avoid the
 Udayakumaran, et al.: IndSPN Shunt guidelines 2021
side‑effects of shunt externalization.
iv. Infected shunt in situ is the least preferable unless
in exceptional circumstances  (specific organisms
like group b streptococcus, meningococcus,
pneumococcus, and H. influenza infection. In all
other circumstances, this strategy has a high failure
and higher morbidity). [55,72]
v. ETV as an option in an active shunt infection is
poorly recommended, especially in shunt‑dependent
hydrocephalus but can be an alternative in carefully
selected situations.[71,75,76]
(IV/V, LOW)
6.2 SURGICAL MANAGEMENT OF OTHER SITUATIONS
COMPLICATING SHUNT INFECTIONS
Surgical management of other situations complicating shunt
infections like associated loculated foci of infections (abscesses,
empyema, and ventriculitis) may be treated on merit  (viz.
conservative or drainage, and lavage) with other
recommendations described.
Discussing other sequelae, including loculated ventricles,
trapped fourth ventricle and so on would be beyond the
guideline subject’s scope.
6.3 TIMING OF INSERTION OF A NEW SHUNT IN A PATIENT
WITH SHUNT INFECTION
RECOMMENDATIONS
i. There is no consensus in the literature on the utility of CSF
values in therapeutic decision‑making, including the timing
of insertion of a new shunt. Therefore, it is recommended
that the trend of improving clinical symptoms and signs,
pleocytosis, CSF glucose, and at least two negative cultures
be documented before inserting a new implant.[70,77]
ii. When a shunt is inserted postinfection, it is recommended
to use a different site and a new implant, although evidence
for the same is lacking.[78,79]
iii. ETV can be used as an option in a patient who has
completed treatment for shunt infection.[71]
(IV/V, VERY LOW)
Section VII
SPECIAL SITUATIONS
7.1 NONSHUNT‑RELATED SURGERIES IN PATIENTS WITH
A SHUNT THAT MAY RISK SHUNT INFECTION.
• Laparotomy without peritoneal contamination, eg,
elective appendectomy
• Other systemic surgeries not involving peritoneal breach,
eg hernia surgery, tonsillectomy
RECOMMENDATION
We do not recommend any particular perioperative antibiotic
prophylaxis or unique shunt manipulation in patients who
undergo clean intraperitoneal surgeries or any surgeries
elsewhere.[80,81] (IV/V, LOW DEGREE)
• L a p a r o t o m y f o r a n y r e a s o n s w i t h p e r i t o n e a l
contamination (eg., Peritonitis, PEG)
RECOMMENDATIONS
S532 Neurology India | Volume 69 | Supplement 2 | November-December 2021
i. Patients with shunt undergoing intraperitoneal surgery
with contamination require externalizing the shunt and
prophylactic broad‑spectrum antibiotics at anti‑meningitic
dosage with added gram‑negative and anaerobic coverage;
Two sterile CSF cultures are obtained. The distal end
should remain externalized until abdominal pathology is
appropriately addressed.[80‑84]
ii. Alternative destinations for the distal catheter in
ventriculoatrial or ventriculopleural or ventriculo‑gall bladder
shunts can be considered, especially when the peritoneum
remains unsuitable after a period of externalization.
iii. The presence of a VPS should not be considered a
contraindication to a percutaneous endoscopic gastrostomy,
and it is safe to do both procedures simultaneously but
waiting may be reasonable.[85,86]
(IV/V, VERY LOW)
7.2 DOES A IMMUNOCOMPROMISED STATE MAKE A DIFFERENCE
IN SHUNT INFECTIONS?
RECOMMENDATIONS
i. The recommendation for antibiotic prophylaxis and
management of shunt infection with typical organisms
remain the same as for immunocompetent individual with
no literature to support extended prophylaxis or treatment
protocol.[10]
ii. If infection with atypical organisms are present, it is better
to remove remove the shunt and treat with two intravenous
antibiotics for 2 months, followed by 2–12 months of oral
antibiotics
iii. Antiretroviral cover improves outcomes in HIV positive
patients with TBM requiring VPS placement.[87,88]
iv. Fungal shunt infections will need to be treated till all
symptoms, signs, CSF, and radiological markers are normal.
Hence, it may need to be continued for several months till
the patient is no longer immunosuppressed and is clinically
well.
v. Use of antibiotics‑impregnated shunts may reduce the risk
of infection in immunocompromised.
(V, VERY LOW)
Section VIII
MANAGEMENT DIFFERENCES IN VA SHUNT
RECOMMENDATIONS
i. In a VA shunt infection, the externalization and new
implant shunt protocol are the same as any shunt infection.
Before the externalization, a detailed transthoracic
echocardiography should be performed to rule out distal
thrombus. In the case of the presence of a thrombus,
externalization of the distal end is contraindicated and
may require additional procedure for managing the
thrombus.[89,90] (III, LOW)
ii. It is imperative to rule out shunt nephritis in the event of
suspected VA shunt infection. Other recommendations are
the same as for any shunt infection.[91] (II, HIGH)
CAVEATS
• Each recommendation has been assigned a level of
evidence and strength of recommendation based on the
evidence available at the time of development of the
guidelines and will require updating when more evidence
 Udayakumaran, et al.: IndSPN Shunt guidelines 2021
becomes available. Lacunae in the existing literature
regarding the management of CSF shunt infection is a
strong rationale for further prospective research into the
subject.
• The consensus approach used in the development of these
guidelines might reflect some biases of the members of
the GDG. Therefore, another group of neurosurgeons
from our country might have arrived at a different set of
recommendations.
This subjectivity and bias are inherent to any evidence of low
certainty.
Even when the evidence is of high quality, the practice
recommendations have to be made keeping in mind the
practice environment of the target audience (Cf: 2.3: Role of
the antibiotic‑impregnated shunt in avoiding shunt infections).
This dilemma of matching the standard of care with the
milieu is precisely why the “biases” of the members of GDG
are desirable. They are needed to interpret the evidence (both
strong and weak) and make recommendations appropriate for
the Indian situation.
• Additionally, we highlight that we have used the GRADE
system, reflecting that all recommendations are actionable.[1]
Nevertheless, a weak recommendation indicates a need
for a shared decision‑making process, whereas a strong
recommendation means that it is unnecessary to provide
options.[1]
• Surgeons should decide whether certain preoperative
(e.g., Regional hair clipping) and postoperative approaches
are appropriate for a given patient, especially when several
children in our country might not adhere to basic hygiene
standards.
Conclusions
Only a few recommendations for preventing and managing
shunt infections reached a high level of evidence (I and II) and
a high degree of strength of recommendation representing the
high and moderate degree of clinical certainty.
Although the committee has made its recommendations based
on evidence and the most pragmatic option, the physician must
tailor the options suitable to the working environment and to
the clinical situation.
Managing active infection is associated with morbidity and
limitations. Hence, perhaps, the best strategy to treat ventricular
shunt infection is to continue our focus on preventing this
significant complication of CSF shunt therapy.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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53. Brown EM, Edwards RJ, Pople IK. Conservative management of
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56. Nau R, Blei C, Eiffert H. Intrathecal antibacterial and antifungal
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58. Nau R, Sorgel F, Eiffert H. Central nervous system infections and
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66. Tamber MS, Klimo P Jr, Mazzola CA, Flannery AM; Pediatric
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75. O’Brien DF, Javadpour M, Collins DR, Spennato P, Mallucci CL.
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 Udayakumaran, et al.: IndSPN Shunt guidelines 2021

ANNEXURE 1

SUMMARY OF LITERATURE REVIEW AND DETAILED LIST OF LITERATURE REVIEWED

This section elaborates on only selected aspects of the main document and, more importantly, enlists the literature reviewed
in detail as a resource for the reader for any in-depth reference.
“GRADE” system of rating evidence and grading recommendation

The “Grades of Recommendation, Assessment, Development, and Evaluation” (GRADE) approach guides rating the quality of
evidence and grading the strength of recommendations in health care. It has important implications for those summarising the
evidence for systematic reviews, health technology assessment, and clinical practice guidelines. GRADE provides a systematic and
transparent framework for clarifying questions, determining the outcomes of interest, summarising the evidence that addresses
a question, and moving from the evidence to a recommendation or decision1.

The Role of consensus?

No system for evaluating evidence and developing guidelines is perfect. GRADE is the most widely used system but has itself
never been validated. “GRADE cannot be implemented mechanically – there is by necessity a considerable amount of subjectivity
in each decision” (Bestpractice.bmj.com). It can also be subjective with two persons evaluating the same body of evidence coming
to different conclusions about its certainty. The consensus method wherein subject experts evaluated the evidence and then
arrived at a consensus as to the strength of the evidence and the recommendations isa proper method of drafting guidelines.
1) The role of consensus was to adopt the recommendation pragmatically to the social milieu and clinical framework, where
necessary, without lowering the level of care.

In the present context, an example of this approach would be antibiotic-impregnated shunt, where the BASICS trial provided
sound evidence on using antibiotic-impregnated shunts (AIS) to reduce infection (Class I evidence)2.

The recommendation in the current guidelines cf: Section 2.3 recommends “The use of an antibiotic-impregnated shunt implant is
desirable.” This was worded considering the initial economic burden that is incurred in the usage of AIS inspite of the economic
benefit gained by avoiding infections.
2) Recommendations are more likely to be weak rather than strong when the certainty in evidence is low when there is a close
balance between desirable and undesirable consequences, substantial variation or uncertainty in patient values and preferences,
and interventions require considerable resources.

It is for t bringing out these, a decision based on consensus seems more practical in an issue like shunt infection with serious
consequences.

The challenge of rigorous science (GRADE system) and western practice (Where most evidence has come from) may not be
applicable as it is in our clinical framework, opening a role for consensus3.

GENERAL FACTORS INFLUENCING SURGICAL SITE INFECTION

Many general factors mandatory are maintenance of glucose4, normothermia, normovolumia, perioperative oxygen (preoperative
patient optimization4) 4-7. Specific issues like proper hand scrubbing before surgery by all team members and surgical site scrubbing
are additionally strongly recommended 6,7 but with no clarity on the conclusions on duration or agent8-10.

Going into details of general recommendations was not a part of this document goals, but these are equally significant issues pertaining to
any Surgical Site Infection guideline(SSI).

SECTION I PERIOPERATIVE AVOIDANCE OF SHUNT INFECTION

1.1 PREOPERATIVE
1.1.1 ROLE OF PATIENT FACTORS
There is insufficient evidence to recommend a specific infant, weight or CSF parameter to direct the timing of shunt placement
in premature infants with posthaemorrhagic hydrocephalus (PHH)11.

Placement of the shunt should be timed when the infant’s age, weight, and overall stability allow12.

There is no evidence to recommend that delaying shunting lowers the risk of shunt infection, even in open spina bifida operated
within 48 hours.

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1.1.2 INFECTIVE FOCUS ELSEWHERE

Systemic Inflammatory Response Syndrome (SIRS) is a marker for possible infection and metabolic rate in patients13. Some
surgeons consider an elevated white blood count or fever a relative contraindication to a VPS placement. SIRS is not associated
with the development of VPS infections and is not an absolute contraindication to placing a VPS14

1.1.4 ROLE OF PREOPERATIVE NUTRITION

Perioperative nutrition is recommended for malnourished patients. Preoperative immunonutrition is suggested in malnourished
patients with cancer scheduled for major surgery 6. Meta-analyses showed that multiple nutrient-enhanced nutritional formulae
were associated with significantly reduced SSI incidence than a standard formula, both in the RCTs and the observational
studies. The quality of the evidence was rated as very low6,7.

The use of enhanced nutrition support is expensive and requires additional work for clinical staff, including expertise from
dietitians and pharmacists. Notably, the availability of these nutrient products is low. When considering this intervention in
the context of a priority assessment approach to reduce the SSI risk, resources and product availability should be carefully
assessed, particularly in settings with limited resources6,7.

1.1.5  IMMUNOSUPPRESSANT DRUGS AND SHUNT SURGERY

Most studies have focused on methotrexate, biological agents (mainly anti-TNF) and corticosteroids. With a low level of evidence,
it is recommended not to suspend these treatments15. Prolonged antibiotic prophylaxis is also not recommended in patients with
immunosuppressive therapy15. Withdrawal of systemic immunosuppressive therapy before major surgery is not recommended,
and the decision to discontinue the immunosuppressive medication should be made individually and involve the prescribing
physician, the patient, and the surgeon6,7.

OTHER GENERAL CONSIDERATIONS

A)  SPECIFIC CONSIDERATIONS

1.1.5 MRSA SURVEILLANCE/SCREENING
The evidence is not unanimous and focuses mainly on cardiac and orthopaedic surgery4,16-19. There is insufficient/low-quality
evidence of nasal decontamination reducing the surgical site infection (SSI) rate in cardiac surgery4,20.

1.1.9 EXPERIENCE IN PAEDIATRIC NEUROSURGERY

George et al., reporting the 24-year experience of a single institution, described an inverse relationship between surgeon volume
and shunt infection rate21. Lund-Johansen et al. demonstrated a statistically significant difference in infection rate, with lower
rates from the more experienced surgeons versus trainees and lesser experienced surgeons 22,23.

In the 2002 Guidelines for Referral to Pediatric Surgical Specialists, written by the Surgical Advisory Panel of the American
Academy of Pediatrics, it is stated that infants with hydrocephalus are “preferably” cared for by a pediatric neurosurgeon. Still,
the authors did not recommend pediatric neurosurgical care for children older than one year unless there are complicating factors
such as congenital heart disease or brain tumours 24.

IS THE TYPE OF TREATING CENTRE IMPORTANT?

Several studies have investigated the relationship of hospital and physician volume to patient outcome. Evidence is vital for some
illnesses and procedures and weak and non-existent for others. It is not clear whether outcomes depend on the experience of
individual practitioners or the experience of a program or institution and whether the experience is accumulated or is reflected
by the current patient volume treated by a physician or institution. Deterioration in expertise from lack of ongoing practice
may also occur. These findings suggest that health care planners must carefully consider where to provide treatment for new
hydrocephalic patients if institutions and surgeons provide only occasional services to these patients25-29

IS TRAINING IN PAEDIATRIC NEUROSURGERY MORE BENEFICIAL?

Some guidelines are available in the literature for a dedicated specialist to handle at least the high-risk group like premature,
infants and children high-risk systemic conditions.

In the 2002 Guidelines for Referral to Pediatric Surgical Specialists, written by the Surgical Advisory Panel of the American
Academy of Pediatrics, it is stated that infants with hydrocephalus are “preferably” cared for by a pediatric neurosurgeon. Still,
the authors do not recommend pediatric neurosurgical care for children older than one year unless complicating factors such as
congenital heart disease or brain tumours24.

IS SURGICAL VOLUME IMPORTANT?

It has been observed that, in general, with greater experience, the complication rates are lesser23. The mortality rate was significantly
lower in patients whose surgery was performed at high-volume hospitals) or by high volume surgeons30.

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 Udayakumaran, et al.: IndSPN Shunt guidelines 2021

While some studies have noted reduced shunt failure and infection rates when shunt placement is performed by a high-volume
surgeon22, others have failed to identify a correlation between surgeon experience and shunt complications31. Although the
procedure is regarded as simple, proper training is therefore necessary. In this context, the absence of complications in the
operations performed by a resident assisted by a specialist is of interest. In conclusion, studies suggest that neurosurgical residents
are assisted by a specialist during several procedures when training in shunt surgery. When residents have gained sufficient
experience to perform surgery alone, they should begin with Normal pressure Hydrocephalus patients since the frequency of
complications is low in these patients.

PERIOPERATIVE
1.1.4  ROLE OF PROTOCOL GUIDED MANAGEMENT AND ENSURING COMPLIANCE
Choux et al. reported a protocol for shunt implantation that was used from 1983 to 1990. It included a series of steps in the
preoperative, intraoperative, and postoperative periods. The infection rate for 1197 procedures (600 children) was 0.17%, compared
with 7.75% for 606 operations before the protocol (1978–1982)32.

Faillace et al. reported a no-touch technique protocol in which the surgeons’ hands did not touch the shunt equipment. In addition,
traffic in the operating room was limited, educated assistants were used, patient preparation steps were followed, the operative
field had two drapes, and surgeons wore double gloves. This approach was used in 60 procedures and reduced shunt infection
to 2.9% from 9.1% (p = 0.058) seen in a previous group of 120 procedures33,34. Another protocol, including antibiotic prophylaxis,
meticulous surgical technique, and complete shunt revision, reduced the infection rate from 9.4% (382 operations) to 5.3% (112
operations)35. In 2007, Pirotte et al.36 reported no infections for 115 procedures performed using a strict protocol of limited implant
and skin-edge manipulation, minimal personnel in the operating room, shunt surgery first in the morning, avoiding CSF leak,
surgery duration less than 30 minutes, and systemic antibiotic prophylaxis.

Shunt prevention protocol bundle37-39,40, the network infection rate decreased from 8.8% before the protocol to 5.7% while using
the protocol (P = .0028; relative risk reduction, 36%), indicating that use of a standardized protocol and reduction in variation
by adherence to a standard protocol is effective at reducing CSF shunt infection rates37. Overall protocol compliance was about
75%, and another 20% followed 10 of the 11 steps.

The authors concluded there is no good evidence that one protocol is better or that anyone step in either protocol is sufficient
alone. The conclusions are based on the impact of the entire protocol (or “bundle”).

Achieving compliance to the protocol is a practical challenge despite a robust protocol. In the WHO surgical checklist study41-43,
compliance with 6 of 19 steps was recorded. Full compliance occurred in 34.2% of patients at baseline and rose to 56.7% after
implementing the protocol. A higher compliance rate was achieved outside of the operating room environment in the NACHRI
study of central line infections43.

SUMMARY OF PERIOPERATIVE PRACTICES AND RELEVANT LITERATURE

• Preoperative Bath/shower6,7,41,44-46
• Surgery first in morning36
• Double Gloving4,47-49
• Intraoperative change of gloves4,50 and change of gloves before handling implant4,51
• Theatre discipline36,52
• Reducing traffic36,45,46,52
• Senior assistants52
• Eliminate scrub technician from the operating room32
• Adhesive transparent plastics on the surgical field4
• Necessary operative materials were gathered and prepared in the OR preoperatively, including shunt hardware remaining
in its sterile packaging36,45,46
• Immersing shunt in antibiotic solution53.
• Washing the surgical wound with anbiotics7,49,54.
• No-touch technique34
• Shorter duration of Surgery52
• Sterile surgical dressing4.

HAIR CLIPPING
The Cochrane review by Tanner et al. 55 and WHO panel on preventing SSI6,7:

• Found insufficient evidence for an effect of preoperative hair removal on rates of SSIs and the relative effects of shaving and
depilation. There is no research comparing hair removal using clippers with no hair removal.
• If it is necessary to remove hair, clipping results in fewer SSIs than shaving with a razor. No trials have compared clipping
with a depilatory cream.

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 Udayakumaran, et al.: IndSPN Shunt guidelines 2021

• There is insufficient evidence on the rates of SSIs when patients are shaved or clipped one day before surgery or on the day
of surgery. There is no research involving the timing of hair removal using a depilatory cream. Hence clipping shortly before
surgery is recommended
• There is no research to indicate whether the place of hair removal (e.g. operating theatre, anaesthetic room or ward area)
affects SSI rates.
• However, if the hair has to be removed to facilitate surgery or the application of adhesive dressings, clipping rather than
shaving appears to result in fewer surgical site infections.

ANTIMICROBIAL COATED SUTURES (AMS)

AMS reduce in vitro bacterial colonization. However, there is controversy over their usefulness. In general, the studies have a
high possibility of bias, low quality, and have potential conflicts of interest. The most recent meta-analysis shows a reduction
in the incidence of SSI with sutures impregnated with triclosan. However, the benefit was only evident with polyglactin 910
sutures and not polydioxanone sutures. NICE, CDC and WHO suggest considering their use in all types of procedures. The WHO
considers it necessary to carry out more studies, analyze other types of antiseptics and consider variables such as availability and
costs, depending on the field in which these sutures are being used4,7.

Wound closure with AMS was associated with a significantly lower shunt infection risk than placebo suture wound closure
during the first six months after surgery in a prospective, double-blinded, randomized controlled trial56.

The apparent efficacy of this intervention lends indirect support to the hypothesis that postoperative bacterial shunt contamination
represents an underrecognized cause of shunt infection. The negligible added cost of AMS maximizes its potential cost/benefit
advantage for various device implant surgical procedures. These findings warrant further investigation in a larger, longer-term,
randomized, and controlled trial4,56.

METICULOUS SURGICAL TECHNIQUE

The meticulous surgical technique appears to reduce shunt infection risk52,57-60. Avoiding CSF leak is also an essential requirement
for avoiding infection36,57.

SECTION 2 ANTIBIOTIC PROPHYLAXIS

2.1. ROLE OF PROPHYLACTIC ANTIBIOTICS FOR PREVENTING SHUNT INFECTION?
Preoperative antibiotics are beneficial in lowering the infection rate in children undergoing shunt surgery for hydrocephalus61-63.
There is a moderate degree of clinical certainty that preoperative antibiotics are beneficial in lowering the infection rate in children
undergoing shunt surgery for hydrocephalus61-63. By combining the various underpowered studies (meta-analysis) results,
preoperative antibiotics for shunt surgery in children were shown to lower the risk of shunt infection.

The organisms most frequently causing infections of VPS are the Staphylococcus species. The causative episodes are coagulase-
negative staphylococci in 80% of cases. Most of the isolated organisms are methicillin-resistant Staphylococcus epidermidis
(MRSE), but using prophylaxis for only prophylaxis gram+ve organisms may not be sufficient as patient tend to have gram –ve
infections in a significant number of cases64. Considering these facts and choosing a broad spectrum IV administrated antibiotic
with good CSF penetration should be the logical choice65. Additionally, it is agreed upon that a hospital antibiogram should
guide the final choice.

The preventive effect of the routine use of surgical antibiotic prophylaxis (SAP) has long been recognized; however, the necessary
duration of SAP to achieve the desired result has been debated. Most guidelines recommend a maximum postoperative SAP
duration of 24 hours, but increasing evidence shows that using only a single preoperative dose (and possible additional
intraoperative doses according to the duration of the operation) might be non-inferior. Despite this, surgeons still routinely
continue SAP up to several days after surgery, leading to serious concerns about antimicrobial resistance risk. Considering
the low quality of the evidence and the overall meta-analysis results (moderate quality), the expert panel, WHO. Guidelines
Development Group on preventing surgical site infection decided to strongly recommend against SAP prolongation and the
widespread risk of antimicrobial resistance6.

Regarding the duration of antibiotics, Ratilal et in their meta-analysis found a benefit of systemic prophylactic antibiotics in
preventing shunt infection, regardless of the patient’s age and the type of internal shunt used. However, after the first 24 hours
postoperatively, the benefit of its use remains uncertain66,67. Therefore, the duration beyond 24 hours is not recommended for
immunocompetent individual, and any deviation from this evidence would not be considered prophylaxis but may be necessary
for particularly vulnerable groups and unusual scenarios, although evidence is lacking. Prolonged antibiotic prophylaxis is also not
recommended in patients with immunosuppressive therapy15.

Timing and route of administration

The effect is not consistent within the different routes of administration that have been analyzed. Therefore, it is uncertain whether
the prevention of shunt infection varies by antibiotic agents, administration routes, timing and doses, or patient characteristics,
e.g. children and adults63. At least is one report suggesting intrathecal vancomycin can reduce shunt infections68.

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WHO panel of SSI6,7 summarised that based on the available evidence, the more precise timing of less than 120 min before
incision cannot be defined, and the widely implemented recommendation of within 60 min before the incision is not supported
by evidence. The half-life of the agent used, the underlying condition(s) of the individual patient (e.g., body mass index, or renal
or liver function), the time needed to complete the procedure, and the protein binding of the antibiotic should be considered
to achieve adequate serum and tissue concentrations at the surgical site at the time of incision and up to wound closure—in
particular, to prevent incisional SSI.

2.2  ROLE OF THE ANTIBIOTIC-IMPREGNATED SHUNT IN AVOIDING SHUNT INFECTIONS

Studies comparing standard shunts with antibiotic-impregnated shunts (AIS) 69-71, two metanalyses 61,66,67,72, AIS were associated
with a significantly lower incidence of infection, compared to silver shunts and standard shunts69. This effect was present across
all age categories. in children, reducing in adults, and being particularly low in the elderly69.

There are significant economic benefits for every shunt infection averted, although cost-effectiveness is greatest in those at highest
risk69. The BASICS trial provided sound evidence on the use of AIS to reduce infection. A previous randomized trial70 compared
AIS with standard shunts, but was underpowered and did not show a significant difference in the risk of infection (relative risk
0·38, 95% CI 0·11–1·30; p=0·12)70. Additionally, systematic reviews and meta-analyses72,73 did not find any high-quality evidence
to support the comparative effectiveness of antibiotic shunts at reducing infection. Complications associated with shunt failures
are expensive to manage74-76. Economic analyses suggest that the use of impregnated shunts that result in fewer complications,
even if more expensive to purchase, could be cost-effective or yield cost savings73,77,78. The cost-effectiveness analysis in BASICS
estimated that although antibiotic shunts cost twice as much as standard shunts, they are expected to be cost-effective overall.
Nevertheless, based on the primary economic outcome, this estimate might be at the expense of additional cases of shunt failures
(for any reason) associated with the use of silver and antibiotic shunts compared with standard ones. The secondary economic
outcome based on the incremental cost per shunt infection averted is relevant because a reduced incidence of infection is expected
to be associated with a reduced need for further surgery and prolonged hospital care.

AIS protective activity was more significant in newborns and specific high-risk subgroups such as children with previous EVD,
posthemorrhagic and post-infective hydrocephalus, and premature, although the conclusion may be weak79. In their retrospective
study, Parker et al. examined CSF infections in several patients with high-risk factors [prematurity, post-meningitis, conversion
of external ventricular drains, prolonged hospital stay]. In all high-risk groups, AIS was associated with significantly reduced
rates of shunt infections71.

Present AIS has certain limitations, including incomplete shunt protection (Spectrum covered by the antibiotics), contraindication
in patients with allergy to clindamycin or rifampin, and significantly increased cost compared with that for nonimpregnated
shunts. It is accepted that even in AIC, the valves are not antibiotic-impregnated, which has to be taken into account. Additionally,
antibiotic-resistant organisms proliferate, it is likely that these catheters will gradually become less effective.

SECTION III DIAGNOSIS OF SHUNT INFECTIONS

3.1 DEFINITION AND ESSENTIAL CRITERIA FOR DIAGNOSIS OF SHUNT INFECTION
No widely accepted gold standard for the diagnosis of shunt infection exists. Worldwide, there is no consensus on the parameters
defining shunt infection, so data specific to shunt infection, not available80. The diagnosis was not the primary objective of most
studies, so the studies could not be graded against each other. Of the 49 articles included in the analysis, nine did not define
infection, nine used cultures alone, nine used cultures and/or symptomatology, and 4 used a combination of cultures, CSF
pleocytosis, and symptomatology. The remainder of the studies used definitions by the CDC (n = 2), Hydrocephalus Clinical
Research Network (HCRN, n = 2) or borrowed elements from these definitions80. The CDC definition of ventriculitis/meningitis is
inclusive and takes culture, signs, symptoms, vitals, and patient age into consideration. Odio et al. defines infection as positive CSF
culture and/or pleocytosis associated with fever, neurological symptoms, abdominal signs or symptoms, or shunt malfunction80.

The HCRN ( Hydrocephalus Clinical Research Network), a collaboration of pediatric neurosurgical centres conducting systematic
investigations in the management of pediatric hydrocephalus, defined shunt infection37, as 1) identification of organisms on
culture or Gram stain from CSF, wound swab, or pseudocyst fluid; 2) shunt erosion (defined as wound breakdown with visible
shunt hardware); 3) abdominal pseudocyst (even in the absence of positive cultures); or 4) positive blood cultures in a child with
a ventriculoatrial shunt.

Definition of pleocytosis
Its unclear about the threshold for defining a CSF shunt infection when relying on WBC counts alone, and what is the evidence
that this threshold is accurate. One would also wonder about the difference in WBC populations, such as the percentages of
lymphocytes and eosinophils affecting the diagnosis of a shunt infection as well47. Symptomatology of shunt infection may be
overlap many of the postoperative and medical scenarios. Additionally, the clinical presentation may differ in each age group.
In contrast to native meningitis, shunt-associated infections often presented nonspecific clinical signs and symptoms (e.g., fever).

In comparison, typical neurological manifestations—such as neck stiffness, a decrease in Glasgow Coma Scale, headache, or
nausea—were present in less than one-half of the episodes. A proportion of patients have no fever or no neurological abnormalities.

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This fact reflects the nature of implant-associated infections, typically caused by low-virulence and slowly replicating organisms
growing on the shunt surface in biofilms, such as coagulase-negative staphylococci common cause shunt-associated infections81.

Culture positive CSF sample may be the gold standard for the diagnosis of shunt infection. Still, a common scenario is CSF
culture being negative in the presence of empirical use of antibiotics before suspecting shunt infection. Hence pleocytosis in an
appropriate clinical scenario may be diagnoses as shunt infection. Many at the time, the surgeon’s clinical judgment will have to
take precedence over the evidence in the diagnosis of shunt infection.

The samples are obtained at the time of catheter externalization. The CSF is transferred to a sterile test tube. Also, 2 ml should be
inoculated into an anaerobic blood culture bottle. The distal catheter tip is also placed in a sterile test tube82. All cultures should
have thioglycolate broth, an excellent medium for the culture of anaerobes. CSF specimen grew bacteria mostly > 3days and
some requiring as long as ten days. Add cultures for anaerobic bacteria at every sampling occasion and prolong the incubation
times for one week or longer82. S.aureus had the shortest incubation period, but Propionibacterium (anaerobic) had an incubation
period of ten days. Routine CSF observation is justified for ten days83,82. The logistics for proper transfer and adherence to technical
standards of microbiological standards must be maintained to avoid false results. Culture of CSF shunt tubing removed at surgery
is associated with a false-positive result in 26% of cases84,85.

Receiving antibiotics decreases detection sensitivity by half but does not prolong the time needed for positive cultures. P acnes
is an anaerobic gram-positive rod commensal to sebaceous glands and hair follicles. Overall, positive culture is often a result of
contamination rather than true infection80.

CSF PMN leucocytosis is a predominant marker of infection. Gm -ve organisms have a high WBC count(neutrophils) P. acnes
infection had a higher percentage of eosinophils. There is a definite pattern of CSF pleocytosis with initial polymorphonuclear
cell leading to mononuclear and then eosinophils. Additionally, there is an associated elevated protein and decreased glucose
compared to serum glucose (Normal range 1/3rd to 2/3rd of serum values).

Blood cultures are an essential part of diagnosis during sepsis and are especially important when a VA shunt is present. Ventriculoperitoneal/
ventriculopleural shunts usually do not yield positive blood cultures. In VA shunts, shunt nephritis occurs because of chronic low-grade
infection resulting in immune complex deposition on the glomerular basement membrane and should also be ruled out.

Abdominal pseudocyst
A pseudocyst is a loculated CSF collection at the terminal end of the catheter formed by peritoneal adhesion or greater omentum
migration in a ventriculoperitoneal shunt. Shunt loculation within the abdomen preventing the peritoneal resorption of CSF occurs
in 0.7 to 10% of patients. The presence of abdominal pseudocyst is taken as a shunt infection, even in the absence of positive
cultures. Pseudocyst can be small, large, non-septate, multiseptate, but it is essential to identify shunt tip within pseudocyst. It
has been suggested that smaller pseudocysts tend to be infected, and larger pseudocysts tend to be sterile. Ultrasound shows a
well-defined sonolucent mass with posterior acoustic enhancement. A non-infected cyst will show uniform echotexture within,
whereas septa may occur in an infected pseudocyst, often having internal echoes or a fluid level. Identifying the shunt tip within
the pseudo- cyst is essential, and the hyperechoic tip must be differentiated from septa86. In a series of 295 pediatric pseudocysts,
the positive culture rate was 41% for those five years and younger, 39% for children between 5 and 10 years old, 16% for patients
between 10 and 15 years old, and only 4% for those 15 years and older. Staphylococcus aureus and S epidermidis are reportedly
the most common culprits. Overall, there is a consensus that not all pseudocysts are infected80.

Csf studies (cell count)

Cerebrospinal fluid leukocytosis in which polymorphonuclear leukocytes predominate is considered a marker for infection.
There are very few studies examining “normal” CSF cell counts in children with shunt tubing. Lenfestey et al. examined the
CSF cell levels in 181 neonates with either a VP shunt or CSF reservoir and compared these counts with those in a group of
neonates without ventricular catheters. There was no significant difference in baseline WBC counts between the groups. In
neonates with a ventricular catheter and infection, there was a mean WBC count of 150 cells/mm3. The authors attempted to
identify the appropriate level of WBC sensitive to infection. A level of 100 cells/mm3 had a sensitivity of 100%, a count greater
than 30/mm3 had a sensitivity of 75%, and a count greater than 6/mm3 had a sensitivity of 73% in this study. Other authors have
similarly recommended a level of 100 WBC/mm3 as a predictor of infection, although the number of cases studied is relatively
small. Gram-negative organisms tend to have a high WBC count with a predominance of neutrophils. P. acnes infections had a
statistically significantly lower percentage of PMN leukocytes (p = 0.002), with a higher peak percentage of eosinophils (p = 0.02)87.
All organisms showed a predictable pattern of cell count progression, except for P. acnes, the initial WBCs were predominately
PMN leukocytes. The peak WBC count generally came a few days after the presentation. Following the initial influx of PMN
leukocytes, all organisms showed delayed peaks of lymphocytes, monocytes, and eosinophils. All organisms showed progression
toward zero over the 14-day treatment period87.

Other CSF markers (CRP, Procalcitonin)

Approximately 6 hours after the onset of infection, interleukin-6 is produced by macrophages to modulate C-reactive protein (CRP)
production by hepatocytes and adipocytes.CRP attaches to phosphorylcholine on microorganisms to help facilitate the complement

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system. The reported sensitivity of CRP varies based on study design and laboratory cutoff from a sensitivity of 75% to 97% and
a specificity of 73% to 80% for shunt infection80. An elevated CSF lactate or CSF procalcitonin (or the combination of both tests)
may aid in diagnosing bacterial CSF shunt infection. For example, an elevated serum procalcitonin may help differentiate between
CSF abnormalities due to surgery or intracranial haemorrhage and bacterial infection since serum procalcitonin is often elevated
in the setting of bacterial infection. However, further study of the utility of these tests in patients with CSF shunt infections is
necessary since some processes can cause both CSF lactate and serum procalcitonin elevations88.

ESSENTIAL CRITERIA FOR DIAGNOSIS OF SHUNT INFECTION

The HCRN ( Hydrocephalus Clinical Research Network)38 defined shunt infection as:
1) Identification of organisms on culture or Gram stain from CSF, wound swab, or pseudocyst fluid;
2) Shunt erosion (defined as wound breakdown with visible shunt hardware);
3) Abdominal pseudocyst (even in the absence of positive cultures); or
4) Positive blood cultures in a child with a ventriculoatrial shunt.

Odio et al. defined infection as positive CSF culture and/or pleocytosis associated with fever, neurological symptoms, abdominal
signs or symptoms, or shunt malfunction80.

CSF culture
CSF can be obtained via shunt tap, lumbar puncture, or when the shunt is externalized, but CSF aspirated from the shunt reservoir
has the highest yield. Therefore, a routine 10-day observation period for CSF specimens is justified for detecting coagulase-negative
staphylococci, Propionibacterium sp. and Bacillus sp83.

3.3 RECOMMENDATIONS FOR GUIDELINES FOR IMAGING IN SHUNT INFECTIONS

Neuroimaging studies are mandatory during patient evaluation for suspected shunt infection. In the context of known infection,
findings of potential importance in neuroimaging include abscess, empyema, evidence of ventriculitis, disproportionate oedema
not explained shunt malfunction and CSF shunt hardware retained from previous surgical procedures. Additionally, they may
demonstrate noninfective complications due to shunt infections, including hydrocephalus, vasculitis, or thrombosis of vessels89,90.

Noncontrast Computed tomography (CT) scanning may help evaluate non-infectious complications, but these are often expected
in the setting of uncomplicated meningitis. In the background of ventriculitis, CT scans will show ependymal enhancement after
the administration of intravenous contrast. However, pachymeningeal enhancement can usually persist postoperatively for months
and should not be confused with a sign of infection91. Magnetic resonance imaging (MRI) is more sensitive than CT for detecting
ventriculitis. Fluid-attenuation inversion recovery (FLAIR) and post-contrast T1 weighted images may be most helpful. Debris
within the ventricles, especially on diffusion-weighted imaging, is the most definitive sign of ventriculitis. Diffusion-weighted
imaging can also be used to detect pus in the ventricular system (visualized as a bright signal) and to differentiate a brain abscess
from malignancy89. Ventricular loculations( non-communicating pockets of CSF), trapped fourth ventricle can be seen secondary
to ventriculitis, evaluated best on MRI91,92.

A neurosonogram can serve the same purpose in a neonate or an infant with open fontanelle. The advantage is that it may be
feasible at the bedside, but the disadvantage is subjective, depends on the sonic window and may miss specific findings like a
subdural collection infective or noninfective.

The diagnosis of CSF shunt infection may be more challenging to establish when the distal portion of the ventriculoperitoneal
shunt is infected. The shunt tap may be normal with negative cultures if a retrograde infection has not yet developed in the
patient. VPS with distal occlusion and without an apparent mechanical cause and no symptoms or signs of infection have been
associated with infection. In these clinical scenarios, an ultrasound or CT of the abdomen may identify CSF loculations at the
shunt terminus, intraintestinal shunts in patients with abdominal symptoms or signs.

Peritonitis can be detected on the CT abdomen, demonstrating inflammatory fat stranding, free fluid, peritoneal thickening,
enhancement, or abdominal abscess.

3.4 RECOMMENDATIONS FOR CULTURE NEGATIVE CSF BUT HIGHLY SUSPICIOUS CLINICAL LAB
Scant literature is available with the recommendation to repeat the CSF sample. Usually, the setting is of a patient on an
antibiotic. The decision may have to based on the clinical scenario and the surgeon’s perspective. If the CSF culture is negative,
symptomatology and signs, proximity to the shunt surgery, and ancillary lab evidence may help make decisions. Additionally,
a repeat sample for CSF culture, maintaining the culture. for observation for at least ten days and a PCR based CSF evaluation
may be an option. Galactomannan may be useful for invasive fungal infections93.

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SECTION IV MANAGEMENT OF SHUNT INFECTION- DRUG THERAPY

ANTIBIOTIC PROTOCOL IN DIAGNOSED SHUNT INFECTION
4.1 BACTERIAL INFECTION
4.1.1 EMPIRICAL ANTIBIOTICS FOR BACTERIAL SHUNT INFECTION
This section draws upon the 2017 Infectious Diseases Society of America’s Clinical Practice Guidelines for Healthcare-Associated
Ventriculitis and Meningitis to base its recommendations. Unfortunately, no studies have specifically looked at the problem of
best empiric therapy for suspected shunt infection. Hence, empiric therapy is directed at the most common organisms which are
likely to cause shunt infection. The most common organisms associated with shunt infection are coagulase-negative staphylococci,
especially Staphylococcus epidermidis, Staphylococcus aureus, Cutibacterium acnes (formerly Propionibacterium acnes- which
causes an indolent infection and may show up in culture only as late as day 10), E.coli, Klebsiella species, Acinetobacter species
and Pseudomonas. Group B streptococcus, meningococcus, pneumococcus, and H. influenza infections are different in that they do
not form the protective slime capsule around their colonies on the shunt, and hence, may be more likely to be successfully treated
with antibiotics alone. The principles used to treat this infection are the same as those used to treat bacterial meningitis, and the
anti-bacterial therapy must be bactericidal. It should be able to cross the blood-brain barrier to achieve high CSF concentrations 94-98.
Agents effective against both gram-positive and gram-negative organisms must be used- vancomycin in combination with
cefepime, ceftazidime or meropenem is recommended by all reviews and guidelines based on the above principles88,94,95.

The 2017 Infectious Diseases Society of America’s Clinical Practice Guidelines for Healthcare-Associated Ventriculitis and
Meningitis recommends adjusting vancomycin dosage based on the serum vancomycin trough concentration, which should be
maintained between 15 and 20 µg/mL in adult patients who receive intermittent bolus administration. Some clinicians administer
vancomycin with a loading dose of 15 mg/kg, followed by a continuous infusion of 60 mg/kg/day. This strategy can be used
in hospitals where serum levels of vancomycin cannot be measured. Monitoring of nephrotoxicity is extremely vital with this
approach because serum levels as high as 30 µg/mL can be achieved. However, this has the advantage of ensuring reasonably high
CSF levels even without intraventricular instillation of vancomycin. When vancomycin is used in higher doses, concomitant use
of nephrotoxic agents such as aminoglycosides and Amphotericin B should be avoided as far as possible88,97,99. Pharmacodynamic
studies suggest that with several beta-lactam antibiotics and vancomycin, the maximum bactericidal activity in CSF was achieved
only when drug CSF concentrations exceeded the minimum bactericidal concentration (MBC) of the causative organism for the
entire dosing interval97. Empiric therapy should also take into consideration local pathogens and the sensitivity of organisms
while selecting antibiotics. If the patient has a previous shunt infection or another site with known organisms and sensitivity
patterns, empiric therapy should include those anti-bacterial agents. Meropenem is probably better reserved for empiric therapy
in situations where hospital-acquired infections by extended-spectrum beta-lactamase-producing gram negative bacilli (ESBL-
GNB) and Acinetobacter baumannii are thought to be highly probable.

Dosage and alternatives in case any of the first line antibiotics are contraindicated are mentioned in Table 1.

4.1.2 DEFINITIVE ANTIBIOTICS IN A PROVEN BACTERIAL SHUNT INFECTION

Once the organism causing the infection has been identified, the treatment should be based on the sensitive antibiotics and their
minimum inhibitory concentration (MIC). Table 2 shows the drugs commonly used for various organisms and their dosage
(Dosages that have been mentioned in Table 1 are not repeated in Table 2). Methicillin-sensitive staphylococci are best treated
with Nafcillin or Oxacillin except in the presence of sensitivity to beta-lactam agents when vancomycin is preferred. Vancomycin
is also the preferred drug for methicillin-resistant Staphylococci when its MIC is 1ug/ml or more. Among the alternative drugs,
Linezolid is often the most effective88. Rifampicin is recommended as an additional treatment for staphylococcal ventriculitis
if sensitive, especially in the presence of retained infected shunt hardware. Except for S.aureus, it has been documented to be
a beneficial adjunctive therapy for staphylococcal shunt infections when removal of the shunt is not being considered as part
of primary therapy100,101. Cutibacterium acnes is an anaerobic, pleomorphic diphtheroid Gram-positive bacillus that causes an
indolent infection that is difficult to identify because it may show delayed growth on culture (more than ten days) difficult to
eradicate with antibiotics alone if the shunt hardware is not removed. Sometimes identification is only possible by broad-range
16S rRNA gene PCR test102. Gram negative bacteria are treated based on the sensitivity reports using adequate doses of antibiotics,
as mentioned in Table 2. In the case of resistant gram-negative organisms, prolonged infusion of meropenem with each dose
administered over 3 hours or as a continuous infusion may help treat the infection102. Combined intravenous and intraventricular
Colistin (Colistemethate sodium, CMS) or Polymyxin B is recommended for multidrug-resistant Acinetobacter species. Polymyxin
B has better in vivo pharmacokinetics and a lesser risk of nephrotoxicity compared to colistin. However, the experience with its
use, especially in children, is less extensive compared to colistin103-106.

4.2  ANTIBIOTICS FOR FUNGAL SHUNT INFECTION

Treatment for fungal shunt infection depends on the organism identified as causative. Details of the dosage used for various
organisms are mentioned in Table 3.
1. Candida ventriculitis is treated with liposomal Amphotericin B, 5 mg/kg daily, with or without oral flucytosine, 25 mg/kg
4 times daily. Once the patient has responded clinically to the initial therapy, treatment can be stepped down to fluconazole,
400–800 mg (6–12 mg/kg) daily. The antibiotic needs to continue till all signs and symptoms and CSF and radiological
abnormalities have resolved107,108. Liposomal Amphotericin B is preferred because it achieves higher CSF concentrations than
other preparations109.

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2. The recommended treatment for Aspergillus ventriculitis and meningitis is voriconazole. The initial two doses at 12-hour
interval should be 9mg/kg for children aged 2-12 years and 6mg/kg for adults. This should be followed by a maintenance dose
adequate to maintain a trough dose of 2-5ug/mL, with 350mg every 12 hours being the maximum allowable dose in children.
Voriconazole interacts with some commonly used antiseizure medications, such as phenytoin and phenobarbitone, leading
to sub-therapeutic levels of voriconazole. Therefore, the use of voriconazole may require a change of antiseizure medications.
Posaconazole and liposomal Amphotericin B are alternatives if the patient is intolerant or refractory to voriconazole and will
need to be continued for several months or till the patient is no longer immunosuppressed and has recovered clinically110,111.

4.3  INTRAVENTRICULAR OR INTRATHECAL ANTIBIOTICS

Treatment of shunt related ventriculitis is dependent on achieving bactericidal concentrations of the appropriately sensitive
drug in the ventricle. Suppose this can be achieved by intravenous administration of the antimicrobial drug, and the patient
responds to this therapy. In that case, there does not seem to be an advantage in instituting additional intraventricular (for
ventricular shunts) or intrathecal (for lumbar shunts) therapy. Theoretically, the intraventricular route of administration helps
bypass the blood-brain barrier. It helps achieve a high concentration of the drug at the site of the infection while reducing the
systemic toxicities of the drug. Thus, drugs such as colistin, polymyxin B, vancomycin, gentamicin, etc., which cannot achieve
adequate CSF concentration without first achieving remarkably high serum concentration, are probably better when instilled
intraventricular or intrathecal and have lower toxicity103,104.

However, no controlled studies are demonstrating the efficacy and safety of IVT or ITC antibiotics. The American Association
of Neurological Surgeons (AANS)/Congress of Neurological Surgeons (CNS) Joint Guidelines Committee concluded that the
available literature was inadequate to recommend the use of IVT/ITC antibiotics in the setting of pediatric shunt infection112. A
Cochrane Review comparing intravenous alone versus intravenous plus IVT therapy for meningitis with or without ventriculitis
in neonates concluded that the addition of IVT increased the relative risk of mortality three-fold and hence, is not recommended
in this age group113. IVT formed the cornerstone of managing 30 shunt infections and resulted in the cure of ventriculitis in 19
of 20 patients who had their shunt removed and replaced either immediately or after about one week after removal. However,
only 3 of 10 patients treated with IVT and intravenous antibiotics without shunt removal responded to the treatment114. 28 of
30 (93%) coagulase-negative staphylococcal shunt infections were successfully treated while retaining the shunt in situ along
with IVT therapy through an additional ventricular access device. A formulation of vancomycin without preservative was used
for intraventricular administration, and the dosage was based on the estimated volume of distribution of the CSF to achieve
concentrations of between 50 mg/L and 80 mg/L. The volume of distribution was calculated according to the following formula:
vancomycin dosage (mg)/X (mL)= peak vancomycin concentration- trough vancomycin concentration/1000 ml, where X is the
volume of distribution. The targeted trough and peak concentrations were 10 mg/L or less and 50 to 80 mg/L, respectively.
Patients with infections caused by enterococci received a combination of vancomycin and gentamicin. The total duration of
therapy of all antibiotics was two weeks.6

When 34 shunt infections were treated with externalization of the shunt along with intravenous plus IVT for 3 to 17 days, there
was rapid (1-6 days) sterilization of the CSF and replacement of the shunt could be done early as opposed to intravenous therapy
alone which failed to sterilize the CSF anywhere from 6 to 37 days115.

Treatment of shunt infection due to multi drug-resistant gram-negative bacteria, especially Acinetobacter, can be challenging and
is associated with high mortality. Several studies have demonstrated the effectiveness of using IVT therapy in such a scenario116,117

The degree of CSF penetration with intravenous colistin is highly variable, and combination with IVT administration is
recommended. Rifampin has optimal CNS diffusion and may have a synergistic effect with colistin against Gram negative bacteria,
such as A. baumannii and P. aeruginosa. Toxicity was noted in 16 cases of 234 patients treated with polymyxins (7%), mostly
presenting as chemical ventriculitis or meningitis in two and nine cases, respectively103. In addition, seizures were reported in
three cases, numbness of extremities in two cases, and cauda equina syndrome in one118.

The mean intraventricular daily colistin dose in survival patients was higher than non-survival, and a dose >180,000 IU was
significantly associated with survival. Another review found a cumulative dose above 1,750,000 IU of ITH/IVT colistin (which
correspond to 125,000 IU once daily for 14 days) is associated with better outcomes103.

For patients with shunt infections due to Candida species and in whom the shunt cannot be removed because it is too risky,
Amphotericin B deoxycholate could be administered through the shunt reservoir into the ventricle at a dosage ranging from 0.01
mg to 0.5 mg in 2 mL 5% dextrose in water96.

PRINCIPLES OF IT/IVC ANTIBIOTICS

• The objective of the dosage is to achieve about 10-20 times the mic generally. The dosage is calculated using the trough CSF
concentration of the drug 24 hours after the first injection. The dose of the drug used for IVT/ITC should be adjusted to achieve
an inhibitory quotient =trough CSF concentration / mic= 10-20. However, this is not available in most Indian hospitals and
hence, may not be achievable94,95.
• When the antimicrobial is injected through a drain in the ventricular or thecal space, it should be clamped for 15-60 minutes

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to allow the medication to equilibrate in the CSF94,95. Infants and children with smaller CSF volume should probably receive
smaller doses94,95.
• The drugs used for IVT/ITC should be preservative-free.
• IVT is used when the shunt is a ventriculoperitoneal shunt, and ITC is used only for lumbar peritoneal shunts

4.3.3 WHAT IS THE OPTIMAL DURATION OF ANTIMICROBIAL TREATMENT FOR SHUNT INFECTION?
1. When the infected shunt is retained or externalized, therapy with IVT/ITC plus intravenous antibiotics should continue for
14 days.
2. When the infected shunt is removed-
a. Infections caused by coagulase-negative Staphylococcus or C.acnes with minimal CSF pleocytosis, normal CSF glucose
and few clinical symptoms or signs should be treated for 7-10days.
b. Infections caused by coagulase negative Staphylococcus or C.acnes with significant CSF pleocytosis, CSF hypoglycorrhachia
and clinical symptoms and signs should be treated for 10-14 days.
c. Infections caused by S.aureus or gram negative bacilli should be treated for 14 days
d. MDR gram negative bacilli may need treatment for 21 days
3. When the CSF cultures are repeatedly positive while on appropriate antimicrobial therapy, treatment should be continued
10-14 days after the last positive culture.
4. When CSF cultures are negative in a situation where shunt infection is strongly suspected, treatment should be continued for
14 days.
5. Fungal shunt infections will need to be treated till all symptoms, signs, CSF and radiological markers are normal. Sometimes
especially in immunosuppressed individuals, this may need to be continued for several months till the patient is no longer
immunosuppressed and is clinically well.

Duration of treatment has varied widely in published papers. There has been no study comparing the effectiveness of different
durations of treatment. The optimal balance between too short a treatment duration leading to recurrence of infection and too long
a treatment duration leading to new infections through the external drains has not been found so far through any systematic study.

Kestle et al. found that among 70 patients with shunt infection from 10 centres, the treatment time varied from 4 to 47 days, and
the shunt reinfection rate was 26%. The mean treatment time was 17.4 days for those who later experienced reinfection compared
with 16.2 days for those who did not. The most common organism (Staphylococcus epidermidis, 34 patients) was associated with
a reinfection rate of 29% and a mean treatment time of 12.8 days for those who suffered reinfection and 12.5 days for those who
did not119. Shimuzu confirmed a similarly high shunt reinfection rate of 10 of 36120.

Two weeks of combined IVT with intravenous antibiotics was adequate to successfully treat 28 of 30 (93%) coagulase negative
staphylococcal shunt infections in patients with a retained shunt18.

Arnell et al. reported that all 34 patients with shunt infections were cured with externalization of the shunt, intraventricular
antibiotics for a median of eight days (range 3-17 days), and simultaneous intravenous antibiotics for median 7.5days (range 4-16
days). Therefore, no further antibiotics were given after shunt replacement82. Wang et al. reported zero reinfections of 15 shunt
infections treated using a protocol which included externalization or removal of the infected shunt and treatment with sensitive
antibiotics after CSF culture turned negative for three days for coagulase negative Staphylococci with normal CSF, seven days
for coagulase negative Staphylococci with abnormal CSF, and ten days for other organisms. They also used a three day “off
antibiotic” period before shunt reinsertion121.

James and Bradley found that all 40 patients with shunt infections caused by a single organism were cured by treating them after
CSF culture return positive with a protocol that involved removing the shunt and 7- 12 days of IVT plus intravenous sensitive
antibiotics the CSF culture turned negative. This was followed by an “off antibiotics “ 24-48 hours before the new shunt was
reinserted. The follow-up period for this study was 1–7 years, with a mean of 3.5 +/- 3 (SD) years114.

Bargiacchi et al. reviewed the literature on the duration of IVT/ITC colistin therapy for ventriculitis. They found that shorter course
<1 week correlated with higher mortality, although they could not eliminate the bias introduced by the severity of illness, which can
also influence the treatment’s duration. They concluded that an IVT/ITC dose of 10mg colistin/day for a minimum of 10-14 days
is probably required for successful treatment of shunt infections by susceptible organisms, especially Acinetobacter species103,104.

Fotakopoulos et al. found that the duration of intraventricular therapy with colistin among survivors (n=23) of ventriculitis
due to MDR organisms was 19+/-8 days compared to 15+/-8 among non-survivors (n=11), although this was not statistically
significant (p=0.46)116.

SECTION V ROLE OF OTHER DRUGS IN SHUNT INFECTION

5.1  ROLE OF STEROIDS
Corticosteroids may have a role in treating CNS infections because of their putative role in reducing the inflammatory response
in the subarachnoid spaces. However, there is the fear that when used in patients with infection, corticosteroids may mask the

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signs of infection, cause worsening of infections, especially fungal infections, and could potentially reduce the permeability of
the blood-CSF barrier to some antimicrobials.

Ricard et al. using serial lumbar CSF and serum vancomycin level measurement in patients with pneumococcal meningitis treated
with high dose continuous infusion of vancomycin (60mg/kg/day) and dexamethasone demonstrated that mean CSF levels are
about 30% of the serum levels and that in 8 patients the CSF level was at least ten times the MIC, in 2 it was eight times MIC and
in one it was 2-fold the MIC. Thus, although reasonably high, these lumbar CSF levels in many may not be adequate to sterilize
ventricular CSF in case of shunt infections, especially if the ventricular catheter is retained122.

The use of corticosteroids in patients with bacterial meningitis has remained controversial despite numerous trials.

Adjuvant corticosteroids were not associated with survival or length of hospital stay in children of any age or in the subset of
children with pneumococcal or meningococcal meningitis in a large multicenter observational study from 2001 to 2006, which
included 2780 children with acute bacterial meningitis122. Another meta-analysis concluded that adjunctive dexamethasone in
treating acute bacterial meningitis does not seem to reduce death or neurological disability significantly122,123.

A Cochrane Review of 25 RCTs involving 4121 participants found that dexamethasone (0.6mg/kg/day for four days) given
just before or at the time of the first dose of antibiotics in patients with community-acquired bacterial meningitis (most
common organisms being Hemophilus influenzae (H. influenzae), Streptococcus pneumoniae (S. pneumoniae), and Neisseria
meningitidis (N. meningitidis)) did not reduce overall mortality. However, subgroup analyses for causative organisms showed
that corticosteroids reduced mortality in S.pneumoniae meningitis (RR 0.84, 95% CI 0.72 to 0.98), but not in H.influenzae or
N.meningitidis meningitis. Corticosteroids reduced neurological deficits and hearing loss among adults and children from high-
income countries with good access to medical services. Corticosteroids reduced severe hearing loss in children with H. influenzae
meningitis (RR 0.34, 95% CI 0.20 to 0.59) but not in children with meningitis due to non-Haemophilus species. Corticosteroids
did not have either beneficial or harmful effects on adults or children from lower-income countries124.

5.2  ROLE OF ANTICONVULSANTS

Like any cerebral infection, shunt infection can initiate seizure potential both in acute admission and in follow-up. The type of
infection, its severity and propensity to cause seizures in the acute phase influence the risk of subsequent epilepsy125.

Class II evidence that in adults, brain infection is associated with an increased risk of subsequent epilepsy. Faillace et al. have
reported that shunt infection can present as new-onset seizure or recurrence of a previously stable seizure disorder in 3 of 706
malfunctioning shunts over three years. Though rare, it is essential to recognize this entity. Management includes treatment for
both the shunt infection as well as for control of seizures with antiepileptic drugs126.

Sato et al. reviewed the literature regarding epilepsy following shunts for hydrocephalus. They found that cerebrospinal fluid and
shunt infections led to an increase in the incidence of seizures in shunted patients from 20-27% in patients without infection to
46-54% in those who have had infections. However, there is no agreement on the role of prophylactic antiepileptics in a shunted
patient127.

Levetiracetam is a suitable drug for controlling seizures because it has the least interactions with the commonly used antimicrobials.

SECTION VI
Surgical management of shunt infection
Temporizing measures during shunt infection
Several studies have reported a high rate of reinfection of newly inserted shunt systems is approximately 14.8%–26%,57,119,128. The
statistically significant factors protecting against CSF reinfection are not identified; complete removal of the infected CSF shunt
system without implanting a new shunt ensures a better prognosis128, but this cannot be the usual treatment for patients with
shunt-dependent hydrocephalus.

To date, only one prospective randomized trial has investigated the outcome of 3 different surgical treatment strategies among
30 children, all receiving antimicrobial treatment. In that study, the outcome was favourable in patients with 1-stage or 2- stage
shunt replacement with temporary external ventricular drainage (cure rates, 90% and 100%, respectively), whereas without shunt
removal, the cure rate was only 30%. Several retrospective analyses underlined these findings. Therefore, the recommended
treatment strategy is a 2- or 1-stage shunt replacement with concomitant intravenous antibiotics. In addition, in 1 study, temporary
externalization of only the peritoneal shunt catheter with subsequent replacement was effective in 10 (91%) of 11 patients81.

Few studies have mentioned ETV as option of temporizing option to reduce reinfection rates, as may be seen in repeat shunt
postinfection120,129,130.

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RECOMMENDATIONS FOR POSTOPERATIVE CARE

How are Patients Monitored for Response to Treatment and managing external ventricular drain/externalized shunt

There is no evidence that monitoring inflammatory markers (i.e., peripheral white blood cell count, erythrocyte sedimentation
rate, or C-reactive protein) is useful in monitoring response to therapy. Patients with healthcare-associated ventriculitis and
meningitis should be monitored for response to treatment based on clinical parameters (strong, low).

Frequent sampling is a part of the protocol of managing the externalized shunt. A study by Williams et al.131 assessed whether the
incidence of ventriculitis changed when CSF sampling frequency was reduced to once every three days. In that study, a prospective
sample of external ventricular drain–treated patients were compared to a historical comparison group at two tertiary hospital
intensive care units. The incidence of ventriculitis decreased from 17% to 11% overall and, in those with proven ventriculitis,
from 10% to 3% once sampling frequency was reduced. In patients with healthcare-associated ventriculitis and meningitis and
an external drainage device, monitoring of CSF cultures is recommended to ensure that they become negative (strong, low). In
patients with no definitive clinical improvement, additional CSF analysis is recommended to ensure that the CSF parameters
have improved and the cultures become negative (strong, low).

IMPLANTATION OF NEW SHUNT

Once the infected CSF shunt has been removed, the optimal timing of shunt reimplantation is unclear. Early placement may
increase the risk of relapse, but a delay in reimplantation may increase the risk of secondary external ventricular drain infection.
Therefore, the timing of reimplantation should be individualized based on the isolated organism, the severity of ventriculitis,
and improvement of CSF parameters and CSF sterilization in response to antimicrobial therapy.

The total duration of antimicrobial therapy is difficult to separate from the timing of shunt reimplantation. Some authorities extend
antimicrobial therapy for several days after shunt reimplantation, whereas others decide on the total duration of therapy based
on obtaining negative CSF cultures and do not extend antimicrobial therapy beyond the time of shunt reimplantation.

In patients with shunt infection caused by coagulase-negative staphylococci and normal CSF findings, negative CSF cultures
for 48 hours after externalization generally confirm that removal of the hardware affected a cure and that the patient can have a
new shunt placed on the third day after removal. A true infection was likely to present if the coagulase-negative staphylococcus
was isolated associated with CSF abnormalities (e.g., CSF pleocytosis, abnormal chemistries). If repeat cultures are negative,
seven days of antimicrobial therapy are usually recommended before shunt placement. However, if repeat cultures are positive,
antimicrobial treatment is continued until CSF cultures remain negative for 7–10 consecutive days before a new shunt is placed.
This approach is also recommended for infection caused by P. acnes

For shunt infections caused by S. aureus or gram-negative bacilli, ten days of antimicrobial therapy with negative cultures are
recommended before shunt placement, although some authorities would consider a 21-day course of therapy when gram-negative
bacilli are isolated.

Some experts also suggest three days off antimicrobial therapy to verify clearing of the infection before shunt reimplantation;
this observation period is optional and not routinely recommended. However, these recommendations have not been rigorously
studied, and some patients may require a longer duration of antimicrobial therapy before a new CSF shunt is placed. Furthermore,
significant variations have been observed in the duration of anti-microbial therapy in patients with CSF shunt infections. Careful
follow-up after reimplantation is also critical to ensure that the patient has been cured.

Regardless of the manner of treatment, CSF shunt infection can recur. In one study, the recurrence rate was 26%, with two-thirds
of cases caused by the same microorganism. The recurrence rate in patients with S. epidermidis shunt infection was 29%. In a recent
study in children, risk factors identified for reinfection were those with complex shunts (multiple shunts placed or any single shunt
with multiple catheters together), an atrial shunt, any complication after the first infection (i.e., shunt malfunction, haemorrhage,
CSF leak), or intermittent negative cultures defined as positive CSF cultures clearing and then returning throughout treatment.
• In patients with infection caused by coagulase-negative staphylococci or P. acnes, with no associated CSF abnormalities and
with negative CSF cultures for 48 hours after externalization, a new shunt should be re-implanted as soon as the third day
after removal (strong, low).
• In patients with infection caused by a coagulase-negative staphylococcus or P. acnes, with associated CSF abnormalities but
negative repeat CSF cultures, a new shunt should be re-implanted after seven days of antimicrobial therapy (strong, low); if
repeat cultures are positive, antimicrobial treatment is recommended until CSF cultures remain negative for 7–10 consecutive
days before a new shunt is placed (strong, low).
• In patients with infection caused by S. aureus or gram-negative bacilli, a new shunt should be re-implanted ten days after CSF
cultures are negative (strong, low).
A period off antimicrobial therapy is not recommended to verify clearing of the infection before shunt reimplantation (strong, low).
A surgical approach other than total shunt removal at initial CSF shunt infection was consistently associated with a higher
hazard of lesser cure and higher reinfection in a studies and suggests standardizing the surgical approach (shunt removal
with EVD placement)132,133.

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SECTION VII SPECIAL SITUATIONS

SURGERIES IN PATIENTS WITH A SHUNT FOR OTHER REASON WHICH MAY RISK SHUNT IMPLANT FOR INFECTION.
Risk for same can be stratified by classifying the type of proposed surgery:
a) Intraperitoneal:
1. With contamination (e.g., peritonitis, abscess, perforation)
2. Without contamination (e.g., Laparoscopic Cholecystectomy, Elective Appendicectomy, PEG, Hysterectomy, salpingo-
oophrectomty)
b) Extraperitoneal: e.g., Hernia repair (TAPP, TEP), vasectomy.

a) Intraperitoneal
Intraperitoneal surgery without contamination can be either Clean (where gut and bladder are not opened, e.g. Hernia Repair) or
Clean-Contaminated (where gut and bladder are opened in a controlled environment without any spillage, e.g. Cholecystectomy,
Appendicectomy). For both the groups, the risk of shunt infection is the same as the risk in other cohorts. The literature review
revealed a very low incidence of shunt-related CNS infection or peritonitis following abdominal surgery without contamination.
In most cases, no special precautions were taken to prevent infection. A retrospective review of 39 abdominal and urological
operations showed the minimal risk for infection over a 2–10 year follow up period in patients undergoing routine clean or
clean-contaminated laparoscopic or open surgery 134. Similarly, a retrospective review of 25 children with VP shunts undergoing
gastrostomy tube placement showed a similar postoperative course and no higher risk of complications within a 90-day follow-
up period than non-shunted children undergoing the same procedure135.

Intraoperative consideration: During surgery, in cases where the distal end of the shunt tube will be encountered, the distal
end can be clamped with a guarded artery clip and wrapped in betadine gauze away from the surgical field an added measure,
and then reinserted before closure. Contamination into the peritoneal cavity needs to be avoided 136. Antibiotic prophylaxis and
duration decided for primary (Gastrosurgical/Urological) procedure remain unaffected with a co-existing shunt.

Intraperitoneal surgery with contamination can be either Contaminated (where gut and bladder are opened and there is spillage
or fresh accidental wounds or non-purulent inflammation, e.g. Cholecystectomy with bile spillage, appendicectomy for perforated
appendix) or Dirty (where there is established infection, devitalized tissue, e.g. abscess, necrotizing infections). The rationale
for this approach is to reduce the chances of shunt infection while maintaining CSF drainage in shunt dependent hydrocephalus
patients. Externalizing the drain reduces the chances of shunt infection while maintaining CSF drainage in shunt dependent
hydrocephalus .patients 137. Till abdominal pathology is appropriately addressed, the distal end should remain externalized 138,139.
Alternative destination for the distal catheter in ventriculoatrial or ventriculopleural or ventriculogallbladder shunts should be
considered.

Ventriculoperitoneal shunt placement should not be considered a contraindication to a Percutaneous endoscopic gastrostomy[PEG
]( Infection risk: 4% ). Simultaneous placement of a PEG tube and VP shunt is safe, efficacious, and cost-effective. Thus, in patients
requiring both a VP shunt and PEG tube, placement of both devices in a single surgical procedure should be considered140 although
waiting may be reasonable according to some other authors141.

Antibiotic prophylaxis in the form of anti-meningitic doses of 3rd Generation Cephalosporin, aminoglycoside and nitroimidazoles
till 2 CSF cultures are sterile should be given for contaminated surgeries. Culture-specific antibiotics should be given in Dirty
surgeries with proven infection.

There is a lack of high-powered and randomized controlled studies to provide a clear evidence base regarding managing patients
undergoing VPS surgery within an abdominal and pelvic surgery setting. Further studies comparing outcomes in externalized
versus non-externalized shunts, open versus laparoscopic approaches, and patients receiving special versus no particular antibiotic
prophylaxis are warranted. These studies are even more clinically relevant due to the increasing numbers of shunted patients
with idiopathic intracranial hypertension undergoing bariatric surgery.

The shunted patient can present challenges in a general surgery setting, and lack of experience with CSF drainage devices may
lead to uncertainty when operating in these patients.

SECTION VIII MANAGEMENT DIFFERENCES IN VA SHUNT

VA shunt is an option for treating hydrocephalus, especially when the peritoneal cavity is not suitable. However, it requires the
implementation of a standardized hygiene protocol for the prevention of shunt infection.

The most usual complications are infection, thromboembolic phenomenon and shunt nephritis. An average VA shunt infection
rate is around 7.1% 142. Organisms are the same as those seen with different CSF distal drainage sites143. 0.7–2.3% of VA shunt
infections are associated with shunt nephritis [S .epidermidis 80% cases]. Shunt nephritis can manifest in these patients as an
insidious progressive secondary renal disease associated with proteinuria, nephrotic syndrome, hematuria, fever, anaemia,
hepatosplenomegaly, nonthrombocytopenic purpura, and hypertension 144.

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Treatment includes removal of VA shunt and temporary EVD with iv antibiotics. Prior to removal, echocardiography should be
done to rule out thrombus 145).

The thrombus may need to be addressed via minimally invasive or endovascular options. Large vegetations may have to be
removed via cardiotomy to reduce embolic risk, as minimally invasive or endovascular options may not be possible in smaller
patients146. Additionally, alternative site of diversion may need to be considered.

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ANNEXURE-II

Table 1: Empiric Therapy‑ Primary drugs and Alternative drugs with Total Daily dose (Dosing interval in hours)
Primary Drug Infants and Children Adults Alternative drug Infants and Children Adults
Vancomycin 60mg/kg (6) 30‑60mg/kg (8‑12) Linezolid Age <12 years: 30mg/kg (8) 1200mg (12)
Age >12: 20mg/kg (12)
(Max dose: 1200mg)
Cefepime 150mg/kg (8) 6gm (8) Aztreonam 120mg/kg (6‑8) 6‑8gm (6‑8)
Ceftazidime 200mg/kg (8) 6gm (8)
Meropenem 120mg/kg (8) 6gm (8) Ciprofloxacin 30mg/kg (8‑12) 800‑1200mg (8‑12)

Table  2: Definitive Therapy‑  Primary drugs and Alternative drugs with Total Daily dose  (Dosing interval in hours)
Organism Primary Drug Infants and Children Adult Alternative drug Infants and Children Adult
Staphylococci MS Nafcillin 200mg/kg (6) 12g (4) Vancomycin * *
Oxacillin
Staphylococci MR Vancomycin * * Linezolid * *
Daptomycin Not defined 6‑10 mg/kg (24)
TMP/SMX 10‑20mg/kg (6‑12) of TMP 10‑20mg/kg (6‑12) of TMP
Cutibacterium Cefotaxime 300mg/kg (6‑8) 8‑12 g (4‑6) Penicillin G 3L units/kg (4‑6) 24 million units (4)
acnes Ceftriaxone 100mg/kg (12‑24) 4gm (12) Vancomycin * *
Linezolid * *
Daptomycin @ @
Streptococcus Penicillin G @ @ Cefepime * *
pneumoniae Cefotaxime @ @ Meropenem * *
Ceftriaxone + @ @ Moxifloxacin Not defined 400mg (24)
Vancomycin * *
Pseudomonas Cefepime * * Aztreonam * *
aeruginosa Ceftazidime * * Ciprofloxacin * *
Meropenem * *
Haemophilus Cefotaxime @ @ Cefepime * *
influenzae Ceftriaxone @ @ Aztreonam * *
Ciprofloxacin * *
ESBL‑GNB Meropenem * * Cefepime * *
Acinetobacter Meropenem * * Colistin# 13mg/kg (12) 13mg/kg (12)
baumannii 1mg=12500IU 2mg/kg (12) 2mg/kg (12)
Polymyxin B#
1mg=10000IU
Other Cefotaxime @ @ Meropenem * *
Enterobacteriaceae Ceftriaxone @ @ Aztreonam * *
Ciprofloxacin * *
TMP/SMX @ @
Staphylococci MS ‑ Staphylococci methicillin‑sensitive. Staphylococci MR‑ Staphylococci methicillin‑resistant. ESBL‑GNB‑ Extended‑spectrum B‑lactamase‑ producing
gram‑negative bacilli. Trimethoprim‑Sulfamethoxazole‑ TMP/SMX. *Dosages which have been mentioned in Table 1 are not repeated in Table 2. @dosage as mentioned
above, #Both Colistin and Polymyxin B need an initial loading dose equal one full day’s dose infused over one hour. Colistin dose must be reduced according to renal
function, but Polymyxin B does not need such dose adjustment.[11

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 Udayakumaran, et al.: IndSPN Shunt guidelines 2021

Table  3: Definitive Anti‑fungal therapy‑  Primary drugs and Alternative drugs with Total Daily dose (Dosing
interval in hours)
Organism Primary Drug Infants and Children Adults Alternative drug Infants and Children Adults
Candida Liposomal 3‑5mg/kg (24) 3‑5mg/kg (24) Fluconazole 12mg/kg (24) 400‑800mg (24)
species Amphotericin B + 100mg/kg (6) 100mg/kg (6) (Except C.kruzei) 16mg/kg (12) 8mg/kg (12)
Flucytosine Voriconazole
Aspergillus Voriconazole @ @ Liposomal Amphotericin B @ @
species Posaconazole ‑ 800mg (6‑12)
@
Dosage as mentioned above

Table 4: The recommended dosage of Antimicrobials for Intraventricular and intrathecal use
Antimicrobial agent Daily Intraventricular Dose Specific organism targeted
Amikacin 5‑50mg (usual 30mg)
Amphotericin B deoxycholate 0.01 mg to 0.5 mg in 2 mL 5% dextrose in water Candida
Colistin (formulated as 10‑15mg (1mg=12500 IU) MDR GNB
colistimethate sodium)
Daptomycin 2‑5mg MRCONS, MDR enterococci
Gentamicin 1‑8mg (Slit ventricle‑2, normal‑4, large‑8); children GNB
may need only 1‑2mg
Polymyxin B 5mg (2mg in children) MDR GNB
(1mg=10000 IU)
Quinupristin/dalfopristin 2‑5mg Vancomycin resistant Enterococcus faecium, MRSA
Tobramycin 2‑20mg
Vancomycin 5‑20mg (Slit ventricle‑5, normal‑10, large‑15‑20) Gram positive cocci

Table 5: Drug interactions between antiepileptics and antimicrobials

Antiepileptic medication Interaction with antimicrobial medication
Phenytoin (PHT) PHT decreases level of voriconazole, posaconazole, gentamicin, and amikacin.
Sulfamethoxazole, fluconazole and chloramphenicol will increase the level of PHT
Rifampicin and ciprofloxacin will decrease the level of PHT.
Phenobarbital (PBT) PBT will decrease level of voriconazole, posaconazole and chloramphenicol.
Carbamazepine (CBZ) Voriconazole and ciprofloxacin will increase the level of CBZ.
CBZ will decrease level of posaconazole and rifampicin.
CBZ increases toxicity of linezolid‑contraindicated
Sodium Valproate (SV) SV will increase level of voriconazole.
Meropenem decreases the level of SV
Levetiracetam No significant interactions

Neurology India | Volume 69 | Supplement 2 | November-December 2021 S555

 Review Article

Access this article online

Quick Response Code:
Clinical Outcome, Cognitive Function,
and Quality of Life after Endoscopic
Third Ventriculostomy versus
Ventriculo‑Peritoneal Shunt in
Non‑Tumor Hydrocephalus
Website:
www.neurologyindia.com

DOI:
10.4103/0028-3886.332271 Manju Dhandapani#, Nishant S. Yagnick1,#, Manju Mohanty1, Chirag K. Ahuja2,
Sivashanmugam Dhandapani1

Abstract:
Background: Endoscopic Third Ventriculostomy (ETV) is increasingly being accepted as the treatment of
choice in place of Ventriculo‑Peritoneal (VP) Shunt for hydrocephalus. However, their differences in cognitive
and Quality of Life (QOL) scores have not been studied much in children.
Objective: To compare the outcome, cognitive function, and QOL between ETV and VP shunt.
Methods: Patients of non‑tumor hydrocephalus treated with ETV or/and VP shunt underwent cognitive
assessment (using modified child MMSE standardized as per the age group) and QOL (using PedsQL as per
the age group in Physical, Emotional, Social, and School Functioning domains) in addition to the outcome of
not requiring additional intervention.
Results: Out of 139 patients, there were 29 infants and 40 children upto 14 years. Among these children, ETV
was the primary intervention in 45, VP shunt in 24, and could be studied for a mean follow‑up of 1.7 years.
Though ETV required lesser additional intervention than VP shunt (19.2% vs. 28.6%) in toddlers and older
children, there was no overall significant difference. Subnormal cognitive scores were noted in 25%, 40%,
and 50% after ETV, single shunt procedure, and multiple shunt procedures, respectively, with no statistically
significant difference. Among the different domains of QOL, the child reported scores in the social domain
were significantly better after ETV than VP shunt (475[+13] vs. 387[+43], P value 0.03), whereas most other
scores were non‑significantly better following ETV.
Conclusion: Patients who underwent ETV show a trend for better clinical outcome, cognitive function, and
QOL with significantly better child‑reported QOL scores in the social domain.
Key Words:
National Institute of Cognitive score, domains, ETV, failure, outcome, QOL, VP shunt
Nursing Education
(NINE), Departments Key Message:
of 1Neurosurgery Endoscopic Third Ventriculostomy may be a better option than VP shunt concerning re‑intervention, cognitive
and 2Radiology, Post outcome and quality of life.
Graduate Institute of
Medical Education and
Research (PGIMER),
Chandigarh, India
H ydrocephalus (HCP) is probably the most
common disorder affecting cerebrospinal
fluid  (CSF) physiology among children, both
shunt) has been the standard treatment for
children with hydrocephalus. [3] Due to the
foreign‑body associated complications, such as
#
Both to be considered
due to developmental and acquired causes.[1,2] infection, extrusion, malfunction, displacement,
first authors.
With an annual incidence of 123 per lakh in low and need for revision, endoscopic third
Address for
and middle‑income countries, HCP causes a ventriculostomy (ETV) has gained much
correspondence: lingering impact on often overlooked cognitive attention over the last decade.[4]
Dr. Sivashanmugam function and quality of life (QOL). [2] CSF
Dhandapani, diversion using ventriculoperitoneal shunt (VP How to cite this article: Dhandapani M,
Department of Yagnick NS, Mohanty M, Ahuja CK, Dhandapani S.
Neurosurgery, Post Clinical Outcome, Cognitive Function, and Quality
Graduate Institute of This is an open access journal, and articles are distributed under the terms of Life after Endoscopic Third Ventriculostomy
Medical Education and of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 versus Ventriculo-Peritoneal Shunt in Non-Tumor
Research (PGIMER), License, which allows others to remix, tweak, and build upon the work Hydrocephalus. Neurol India 2021;69:S556-60.
Chandigarh, India. non‑commercially, as long as appropriate credit is given and the new
creations are licensed under the identical terms. Submitted: 01‑Jul‑2021 Revised: 10-Oct-2021
E‑mail: ssdhandapani. Accepted: 12-Oct-2021 Published: 11-Dec-2021
neurosurg@gmail.com For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com

S556 © 2021 Neurology India, Neurological Society of India | Published by Wolters Kluwer - Medknow
 Dhandapani, et al.: Outcome, cognitive, and QOL scores after ETV and VP shunt
Endoscopic Third Ventriculostomy (ETV) enables the free flow
of third ventricular CSF to the subarachnoid space, bypassing
any distal obstruction. The advent of modern fiber optics
and high‑definition cameras have popularized endoscopic
interventions as an effective alternative to shunt procedures,[5]
mainly because a successful procedure freed the patient from
a life‑long implanted device, albeit with potential cognitive
issues due to forniceal handling.[6,7]
Outcome assessment in the management of hydrocephalus
has hinged upon multiple criteria, including post‑operative
symptomatic relief, radiological changes in ventricular
size, revision procedures, neurological deficits, radiological
complications, and infection rates.[8,9] While many studies
on adults have noted ETV to be significantly associated with
better clinical outcomes and fewer revision procedures, there
is a paucity of data on cognitive outcomes and QOL.[8,10] This is
especially even scanter among children, as the standardization
of results across various age groups or pathologies has hindered
any meaningful comparison.
This study aimed to assess the surgical outcome, cognitive
function, and QOL and compare ETV and VP shunt.
Methods
Children up to 14 years of age undergoing VP shunt
or ETV for symptomatic HCP in the department of
Neurosurgery, Postgraduate Institute of Medical Education
and Research (PGIMER), Chandigarh, India, from 2016 to 2017
were included in the study, with appropriate ethical clearance.
Patients with tumors pending surgical excision and those with
any co‑morbidity affecting cognitive function were excluded.
Hydrocephalus outcome was assessed at least 3  months
post‑treatment. ‘Not requiring additional intervention
associated with HCP’ during the whole follow‑up period was
considered for successful surgical outcomes. This includes the
non‑functioning of ETV and any indication of shunt revision
such as infection, shunt block, shunt migration, and abdominal
pseudocyst formation.
Modified child mini‑mental status examination developed by
Jain and Passi[11] was used to assess the children’s cognitive
function aged 3  years and above. The tool consists of items
under the domains of orientation, attention and concentration,
registration and sensory perception, recall, and language. The
maximum score on the scale is 37, and the scale is standardized
as per the child’s age. The ‑2 standard deviation (SD) scores are
24, 28, 30, and 35 for age groups three to five, six to eight, nine
to 11, and 12‑14 years. Any score less than these was considered
abnormal. To make data comparable between ETV and VP
shunt, the difference between an individual patient score and
the minimum standard cognitive score (‑2 SD) for that group
was calculated and named the ‘cognitive deviation score.’
QOL was assessed on children over  2  years of age using
the PedsQL 4.0 generic core scales by Varni et al.,[12] which
evaluates the age‑appropriate physical, emotional, social, and
school functioning over the previous month. The PedsQL
Measurement Model is an integrated method to measure
health‑related quality of life  (HRQOL) in healthy children,
adolescents, and children with acute and chronic health
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S557
conditions. The Likert scale items are reverse scored (to avoid
casual scoring and agreement bias) and linearly transformed to
a zero to 100 scale so that higher scores indicate a better QOL.
Up to 4 years of age, only the parents reported on their toddlers’
QOL. Older children and teens scored their QOL directly and
included the parents’ report as a proxy for their child.
Statistical analysis was done using SPSS17 software (IBM Corp.)
to determine the differences in surgical outcome, cognitive
function, and QOL between ETV and VP shunt. Chi‑square or
Fisher’s exact test was used to compare proportions wherever
appropriate. Independent samples t‑test was used to compare
continuous variables between both the categories. Two‑sided
significance tests were used throughout, and a value of
P value ≤ 0.05 was considered significant.
Results
Out of 139  patients who underwent surgical treatment for
HCP, 29 were infants, and 40 were toddlers and children up
to 14 years. Among these kids, ETV was done as the primary
intervention in 45 and VP shunt in 24.
Over a mean follow‑up period of 1.7  years, 16 kids out of
69 (23%) needed additional intervention, resulting in an overall
success rate of 77%. The further intervention was necessary for
ten of the 45 (22%) who underwent ETV, compared to six of
the 24 (25%) who underwent VP shunt. Toddlers and children
showed a greater failure rate after VP shunt (28.6% vs. 19.2%),
whereas infants showed a higher failure rate after ETV (26.3%
vs. 20%), though statistically not significant [Figure 1].
Among those with only ETV or VP shunt, subnormal
cognitive scores were noted in 25% and 45%, respectively. The
cognitive dysfunction was 50% among those who underwent
multiple shunt procedures and 40% after single VP shunt
surgery [Figure 2]. These differences could not show statistical
significance due to the small numbers of patients. The mean
cognitive deviation from the minimum standard scores was
non‑significantly better after ETV (0.13 [±+1.6]) compared to
VP shunt (‑2.64[+2.9]) (Figure 3).
A comparison of QOL scores in different domains between
patients who underwent ETV and VP shunt is shown in
Table 1. The mean of all QOL scores was non‑significantly
Figure 1: Need for Re-intervention following VP shunt and ETV
 Dhandapani, et al.: Outcome, cognitive, and QOL scores after ETV and VP shunt

Figure 2: Prevalence of Subnormal Cognitive Scores

Figure 3: Comparison of Cognitive Deviation between VP shunt and ETV

greater after ETV than VP shunt  (85  [+2.6] vs. 79.6  [+5.4]).
Both parent‑reported, as well as child‑reported QOL scores, Table 1: QOL Scores: VP Shunt versus ETV
showed a similar better trend after ETV. Among various QOL domain VP Shunt ETV P
domains, the child‑reported QOL scores in the social domain Overall 79.6 (±5.4) 85 (±2.6) 0.10
were significantly better in those who underwent ETV than VP QOL‑PR (Parent Reported) 77.7 (±5.6) 84.6 (±2.7) 0.15
shunt (475[+13] vs. 387[+43], P value 0.03). All the scores, except QOL‑CR (Child Reported) 86 (±6.5) 88.9 (±2.9) 0.11
the child‑reported emotional domain, were higher among kids OL‑PR‑Physical 613 (±71) 663 (±35.3) 0.25
who underwent ETV. QOL‑PR‑Emotional 450 (±18.4) 490 (±5.4) 0.36
QOL‑PR‑Social 370.5 (±49.1) 423.6 (±23.3) 0.36
Discussion QOL‑PR‑School 236 (±79.3) 325 (±33.7) 0.24
QOL‑CR‑Physical 716 (±58) 755 (±29) 0.25
Managing hydrocephalus has been a perplexing challenge QOL‑CR‑Emotional 500 (±0) 461 (±22) 0.31
due to the varied etiologies, CSF flow pathomechanisms, and QOL‑CR‑Social 387 (±43) 475 (±13) 0.03*
presentation with no clear, typical culmination.[13‑15] QOL‑CR‑School 316 (±101) 352 (±30) 0.26
*Significant
ETV and VP shunt did not show any significant difference in
re‑intervention rates among our patients, though the benefit The focus of outcome assessment in many neurosurgical
was more for ETV in toddlers and older children, whereas specialties has crossed the conventional surgical failures to
encompass broad‑based cognitive and functional status of
VP shunt was better in infants. A limited number of patients
patients.[23,24] Neurocognitive deficits are well reported in
probably could not elicit any statistical significance. The
children with hydrocephalous[25,26] due to brain parenchymal
higher failure rate of ETV in infants may be due to anatomical
dysfunction.[21] Although the detailed etiopathogenesis and
reasons that limit the functioning of the ventriculostomy and
nature of the neurocognitive deficits in hydrocephalus are not
the compliance of prepontine subarachnoid space. However,
fully known, numerous factors such as etiology, age at onset,
VP shunt drains CSF regardless of anatomy. However, several
raised intracranial pressure, the rate of ventricular enlargement,
meta‑analyses have yielded good evidence in favor of ETV ventricular size, the duration of hydrocephalus, coexisting
concerning complications, infection, reoperation, duration of pathological changes, and shunt complications, have been
surgery, and hospital stay among toddlers and older children shown to influence cognitive function. Impaired cerebral blood
with non‑communicating hydrocephalus.[8,16] Piatt et al.[17] in flow, alterations of neuronal cell metabolism, axonal loss, and
2008 have reported a shunt failure rate of 38% in children, pathological neurotransmission can also be the reasons for
which is higher as compared to our study where the shunt cognitive deficits of children with hydrocephalous.[26] There
failed among 20% in infants and 29% in other children. Shunt can be neural circuit alterations due to damage of nerve cell
failure is reported to be higher in children, especially during processes and synaptic contacts in the hydrocephalic cortex,
the first 6 months after a shunt.[18] Though ETV is said to have which may also cause the weakening of intellectual functions
a higher initial failure rate than shunt, the long‑term success and learning disabilities in children with hydrocephalus.[27,28]
rate is probably better after ETV.[19] Serious complications in
children who underwent ETV are low.[20] The lower failure rates Both ETV and VP shunt are noted to improve cognitive
and infection rates were reported by many authors in children function in children with hydrocephalus. Warf et al.[21] have
who underwent ETV compared to shunt. Warf et al.[21] in 2009 reported improvement in neurocognitive function in children
and others have, however, noted similar infection rates.[22] with hydrocephalus after shunt as well as ETV, with a

S558 Neurology India | Volume 69 | Supplement 2 | November-December 2021

 Dhandapani, et al.: Outcome, cognitive, and QOL scores after ETV and VP shunt
non‑significantly better neuro‑cognitive function in children
who underwent ETV.[29] While 40% of the children after single
shunt surgery and 50% of the children after multiple shunt
surgery developed cognitive dysfunction, only 25% of those
who underwent ETV had cognitive deficits in our study. The
higher proportion of patients with cognitive deficits in multiple
shunt surgery shows that the number of times a patient
experiences an intervention also is an essential determinant
of outcome.
We did not find any significant difference in QOL in children who
underwent ETV or shunt, except in the social domain, better in
the ETV group. However, overall and domain‑wise, QOL scores
were better in children who underwent ETV. The higher QOL
score for ETV patients may reflect freedom from a prosthetic
device like a shunt. While shunt function depends on pressure
valve mechanisms, ETV is free of such dependency and utilizes
the body’s homeostatic mechanism leading to a more natural
CSF flow. Many authors have similarly reported similar QOL
in infants and children who underwent ETV and shunt.[20,9,10]
The results for QOL assessment mirror those for cognitive
assessment and are likely interlinked. Similarly, the higher
failure rate in children requiring further surgical intervention
may also explain the higher cognitive deficits and poorer QOL
in children who underwent shunt. Prakash et al.[30] in 2018
have reported that QOL of children who underwent VP shunt
is adversely affected in different domains but the highest in
the cognitive domain, which shows its impact on QOL. The
study also reported poor QOL in children who underwent
multiple surgeries. The repeated surgery in a child can result in
physical, psychological, and financial burdens in both children
and parents, which may directly or indirectly affect the QOL
of the children.
Not having an extended follow‑up is a limitation of
our study. Though not significant due to the smaller
sample size, the lesser failure rate, cognitive deficits, and
better QOL in children who underwent ETV demand
more elaborative time-trend data analysis from LMICs,[31]
which bear the most brunt of hydrocephalus and possibly
shunt‑related complications. [32] The underlying cause of
cognitive impairments such as perfusion deficits seen in
other pathophysiology, need to be fully evaluated.[33,34] The
findings also highlight the scant rehabilitation support in
India[35] and urge towards improving cognitive rehabilitative
measures in children who underwent surgical treatment for
hydrocephalous (ETV or shunt) to enhance their QOL.[36]
Hence, a multidisciplinary approach involving neurosurgeons,
pediatricians, nurses, neuropsychologists, and physiotherapists
must be implemented for children undergoing HCL treatment.
In conclusion, ETV has significantly better child‑reported QOL
scores in the social domain. Failure rate and other parameters
did not show a significant difference, despite ETV having
better scores.
Ethical approval
Performed as per the ethical standards of the IEC of PGIMER.
Declaration of patient consent
Informed consent obtained from participants.
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S559
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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 Review Article

Access this article online

Quick Response Code:
Natural History, Treatment Outcomes
and Quality of Life in Idiopathic Normal
Pressure Hydrocephalus (iNPH)
Albert M Isaacs1,2, Mark Hamilton1,2,3
Website:
www.neurologyindia.com

DOI: Abstract:
10.4103/0028-3886.332281
Background: The natural history and treatment outcomes in adult patients with hydrocephalus is a broad and
heterogeneous topic that encompasses the natural history of the various subtypes of adult hydrocephalus
with or without treatment; their surgical operative results, including symptom improvements, treatment
failure, short‑ and long‑term complications, and reoperations; and morbidity, mortality, and patient‑centered
health‑related quality of life (HRQoL).
Objective, Methods, and Materials: The objective of this review is to present a current update on the
natural history and treatment outcomes, including QoL, for adults with hydrocephalus with a focus on patients
with idiopathic normal pressure hydrocephalus (iNPH). A nonsystematic review of relevant literature was
summarized.
Results and Conclusions: The natural history for untreated patients with iNPH is poor, with both increased
mortality and morbidity. It is strongly recommended that practitioners follow established guidelines to select
patients with suspected iNPH while using objective measures of gait, balance, and cognition for consideration
of treatment with a CSF shunt. Other factors such as patient‑related medical comorbidities or frailty may need
to be factored into the decision‑making process before surgical treatment is offered. As a rule, failure to select
patients based on the identified guidelines will result in a significantly lower positive response to treatment
with a CSF shunt. Over 90% of iNPH patients who undergo CSF‑shunt treatment demonstrate symptomatic
relief after surgery, and long‑term studies have shown that in most patients, the clinical improvements are
long‑lasting, with over 70% demonstrating improvement longer than 6 years after treatment. There is no
evidence to support the routine use of endoscopic third ventriculostomy (ETV) to treat patients with iNPH.
There is limited data regarding HRQoL in patients with iNPH. In addition to objective measures of outcomes
focused on gait and cognition, it is equally important for future studies to assess patient‑centered subjective
measures of HRQoL.
Key Words:
Adult, ELD, elderly, external lumbar drain, guidelines, health‑related quality of life, HRQoL, hydrocephalus,
idiopathic normal pressure hydrocephalus, iNPH, LP, lumbar puncture, outcomes, shunt, ventriculoperitoneal
1
Division of shunt
Neurosurgery,
University of Calgary,
Key Message:
Calgary, Alberta,
The natural history of untreated iNPH is very poor and outcomes are good when patients are selected for
Canada, 2Calgary Adult
shunt treatment using established guidelines and modern surgical techniques.
Hydrocephalus
Program, 3Department
of Clinical
Neuroscience,
University of Calgary,
H ydrocephalus is a debilitating neurological
condition that affects approximately every
88 per 100,000 pediatric individuals and 175 per
pressure dynamics. While the pathophysiology
of hydrocephalus is not well characterized,
the ventricular distension occurs as a result of
Calgary, Alberta, 100,000 adult persons worldwide.[1] However, impaired cerebrospinal fluid (CSF) turnover
Canada the prevalence of iNPH in those >80 years of age due to an imbalance between its production and
may approach 5%.[1] Hydrocephalus clinically resorption into the systemic circulation.[3]
manifests with a wide range of symptoms that are
attributable to cerebral dysfunction in the context While hydrocephalus can present at all stages of
Address for of abnormally distended cerebral ventricles[2] that life, there are age‑related nuanced differences in
correspondence: are often associated with abnormal intracranial
Dr. Mark Hamilton,
Foothills Medical How to cite this article: Isaacs AM, Hamilton M.
Centre ‑ 12th Floor This is an open access journal, and articles are distributed under the terms Natural History, Treatment Outcomes and Quality of
Neurosurgery, 1403 – 29 of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 Life in Idiopathic Normal Pressure Hydrocephalus
Street NW, Calgary, License, which allows others to remix, tweak, and build upon the work (iNPH). Neurol India 2021;69:S561-8.
Alberta, T2N 2T9. Canada. non‑commercially, as long as appropriate credit is given and the new
creations are licensed under the identical terms. Submitted: 27‑Jul‑2021 Revised: 23-Oct-2021
E‑mail: mghamilton. Accepted: 25-Oct-2021 Published: 11-Dec-2021
hydro@gmail.com For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com

© 2021 Neurology India, Neurological Society of India | Published by Wolters Kluwer - Medknow S561
 Isaacs and Hamilton: Outcomes for idiopathic normal pressure hydrocephalus
the etiology, clinical presentation, and treatment outcomes.
As such, hydrocephalus is commonly classified into pediatric
and adult subtypes, distinguished by whether the patient is
younger or older than 18 years of age at the time of diagnosis,
respectively. Adult hydrocephalus can be classified into
primary or secondary subtypes, representing congenital forms
and those with hydrocephalus that develop as a result of an
antecedent event, such as hemorrhage, trauma, infection,
or tumor, respectively.[4] Adults who were diagnosed with
hydrocephalus before turning 18 years old have recently been
classified into a “transitional hydrocephalus” subtype as they
present unique treatment and psychosocial challenges.[4,5]
Adults older than 65 years presenting with a clinical triad
of gait disturbance, cognitive impairment, and urinary
incontinence, as well as having radiographic evidence of
abnormal ventricular distension that is not attributable to
age‑appropriate cortical atrophy (ex vacuo) or an obstructive
pathology, without an identifiable antecedent event, or
other leading differential diagnoses to explain the patient’s
presentation, may be diagnosed with idiopathic normal
pressure hydrocephalus (iNPH). [4,6,7] The prevalence of
hydrocephalus in the elderly population (age 65 years or older)
is significantly higher than in other age groups, affecting a
minimum of 175/100,000 individuals globally and increasing
to 5% of individuals ≥80 years of age., with the majority of
people having iNPH.[1]
The mainstay treatment of adult hydrocephalus is CSF
diversion from the ventricles by using CSF‑shunting devices
into extracranial compartments such as the peritoneal cavity,
right atrium of the heart, gallbladder, and lungs.[8‑10] Endoscopic
third ventriculostomy, which diverts the ventricular CSF into
the subarachnoid space, is also a viable option but has very
specific indications[2] and has no role in the routine treatment
of patients with iNPH.
Once a person with suspected iNPH symptoms (e.g., gait
disturbance, cognitive impairment, and urinary incontinence)
with radiographic ventriculomegaly is identified, it is essential
to utilize an objective process to select which patients will
most likely respond positively to treatment with a CSF shunt.
There are numerous reviews that provide the details associated
with currently available guidelines[6‑7,9] The key principles
necessary to sort through the selection of which patients are
appropriate for surgery include 1) a need to first evaluate
patients for the possibility of other or coexistent diagnoses
that may be associated with the presenting symptoms, 2)
assess and document their baseline function (gait, cognition,
and urinary continence) with objective measures,[6,7] and 3)
undertake temporary removal of a large volume of CSF by
lumbar puncture (LP) or external lumbar drainage (ELD),
which can be considered a temporary shunt mimic, followed
by the retesting of the patient’s baseline function (gait and/
or cognition). Patients who demonstrate clinically significant
improvements in their baseline function following CSF removal
can be offered permanent CSF diversion surgery.[6‑7,9] The
differences in sensitivity and specificity between a large‑volume
LP and ELD for assessment of the iNPH patient are complex.
However, it is likely that ELD is more sensitive and specific
than a large‑volume LP.[6,9] Alternatively, a CSF infusion test
may be used to assess the patient’s CSF outflow resistance,
S562 Neurology India | Volume 69 | Supplement 2 | November-December 2021
often followed by a large volume LP, with a sensitivity and
specificity to predict suitability for CSF shunt surgery likely
intermediate between the large volume LP and ELD.[11]
While there is extensive literature detailing the diagnosis,
treatment, and management of adult patients with
hydrocephalus, there are significant variations in the reported
surgical outcomes., Historically, the outcomes of CSF diversion
surgery for the treatment of hydrocephalus have been abysmal,
with treatment failure rates of approximately 50% in the first
2 years of surgery. However, in the last few decades, significant
improvement in the accuracy of diagnosis, patient safety, and
surgical precision has led to improved perioperative patient
outcomes, yet there remains a lag of reported long‑term patient
outcomes and health‑related quality of life (QoL) outcomes
and measures.
The objective of this review is to present a current update on
the natural history and the treatment outcomes of adults with
hydrocephalus. The topic dealing with the specific details of
shunt and endoscopic surgical technique have been previously
elaborated and are not addressed in this paper.[6‑9] In addition,
while other age‑appropriate comorbidities and frailty may
influence the decision process regarding whether to proceed
with CSF‑shunt surgical treatment, these complex issues, while
relevant, are beyond the scope of this paper and are addressed
in previous publications.[6‑7,9]
It is important to appreciate that the natural history and
treatment outcomes in adult patients with hydrocephalus is
a broad and heterogeneous topic that encompasses various
subtypes of adult hydrocephalus with or without treatment;
their surgical operative results, including symptoms
improvement, treatment failure, short‑ and long‑term
complications, and reoperations; and morbidity, mortality, and
patient‑centered health‑related QoL (HRQoL). To help manage
this task, this review will focus predominately on the condition
of iNPH. While there are some obvious differences between
patients with iNPH and some of the other types of adult
hydrocephalus, there are many similarities to other forms of
chronic adult hydrocephalus conditions as relates to the clinical
presentation, management approach, and immediate response
to treatment. Thus, while there may be some differences
regarding long‑term treatment outcome expectations, the
diagnosis and management strategies presented for iNPH
patients can be successfully applied to other subacute and
chronic clinical subtypes of hydrocephalus in the adult patient.
Controversies and Variability of Outcomes
Assessments in iNPH
To clinically diagnose iNPH, a patient must be
elderly (≥60 years), have abnormal ventricular enlargement
demonstrated on cranial computed tomography (CT) or
magnetic resonance imaging (MRI), and must have at least one
of the iNPH triad of neurologic symptoms: gait and balance
disturbance, cognitive impairment, and urinary urgency
and/or incontinence. Many experts consider gait and balance
impairment as essential symptoms.
An ideal outcomes assessment in any clinical condition
should include objective measures that are both sensitive and
 Isaacs and Hamilton: Outcomes for idiopathic normal pressure hydrocephalus
specific to the condition, can be easily utilized in the target
patient population, are reliable and easy to replicate, can be
used to establish the patient’s baseline prior to intervention,
then repeated at serial time points after the intervention
to assess for response or failure of intervention, short‑ and
long‑term. In iNPH, there are several measures that can be
utilized to independently assess gait, balance, cognition, and
urinary continence. Gait and balance assessment measures
that can be used in iNPH patients include, but are not limited
to, the 10‑m straight walk test, timed up‑and‑go test, Tinetti
assessment tool, and the Boon scale.[12‑15] A wide variety and
combinations of neuropsychological batteries have been used
to assess cognition in iNPH, including the Montreal Cognitive
Assessment, Symbol Digit Modalities Test, Mini Mental Status
Exam, National Adult Reading test, and the Weschler Adult
Intelligence sometimes in conjunction with the Beck Depression
Inventory. The Lawton ADL/IADL scale and the Modified
Rankin Scale (mRS) can be easily undertaken to provide a
measure of overall patient function.[16,17] Assessment of urinary
incontinence is often subjective and obtained through history
rather than physical examination. The Overactive Bladder
Questionnaire‑Short Form (OAB‑q SF)[18] can be used to more
reliably assess the severity of bladder symptoms and the effect
on a patient’s QoL.
While many of the tests are effective for the assessment‑specific
focused iNPH outcomes, it is important to note that they are
often not comprehensive enough to capture all the potentially
important changes in patient symptoms. It must be noted
that regardless of the test chosen, it is essential to assess each
patient under conditions that are standardized and have
minimal variability between measurements. Even within
discrete measures, it is often necessary to utilize a variety of
assessment tools to capture small improvements in symptoms
that may otherwise be missed. For example, the mRS scale
is commonly used in assessing iNPH to assess disability
on a Likert scale ranging from 0 for no symptoms to 5 for
severe symptoms requiring constant need for care. However,
the mRS is only capable of providing a general assessment
of global functionality, and as such, patients experiencing
marginal but clinically important functional improvements
such as advancing from using a walker only needing a cane
for mobility may not have this improvement reflected in an
unchanged mRS score.
Because most of the utilized outcome measures are not
fine‑tuned to iNPH, the development of certain iNPH‑specific
outcome measures has occurred. While it is still considered
important to report patient outcome measurements (e.g. gait
velocity) as discrete values, the use of focused iNPH scales
in clinical practice can potentially provide a more nuanced
clinical, patient‑relevant outcome measure. Currently, there
are two major iNPH scales, the European[19] and Japanese
scales,[20] with each testing the same triad (gait, cognition,
and continence) but with differences that do not make them
ideally comparable. As such, one cannot overemphasize the
importance to pay critical attention to the outcomes been
examined as well as the scoring system been used by studies
when discussing hydrocephalus outcomes. For example,
in the Japanese SINPHONI trial[21] that assessed 100 adult
hydrocephalus patients undergoing lumboperitoneal shunt
surgery, 69% of patients improved on their mRS score, whereas
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S563
77% demonstrated improvement when the Japanese Gait
Scale[20] was used. Similarly, in the European multicenter trial
of 143 patients, 69% of patients improved on the mRS scale,
but on the European iNPH scale,[19] 56%, 63%, 66%, and 77%
demonstrated improvement in balance, continence, cognitive
and gait domains, respectively.[19]
Currently, there are two major guidelines available for the
diagnosis and management of iNPH that can be used as a
benchmark for assessing outcomes: the international[22,23] and
Japanese[24‑26] guidelines. However, while both guidelines
are similar, they each use slightly different outcome
measures to objectively assess patients. However, while some
reported outcomes in the literature are based on established
guidelines, far more than half of the existing literature is not
guideline‑based.[27‑32] Consequently, there remains significant
variability in the literature on the outcome measures used
to assess iNPH patients, leading to wide ranges of reported
outcomes. It is strongly recommended that practitioners follow
established guidelines to select patients with suspected iNPH
for consideration of treatment with a CSF shunt.[6‑7,9,22‑26]
In addition to the variability in reported outcomes due to
having a wide variation of tests, scales, and guidelines, the
outcomes associated with the surgical treatment of patients
with iNPH have also significantly evolved and improved
over time. Complications associated with shunt surgery
in the elderly have also declined significantly in the past
30 years. Historically, there had been a wide variation in the
reported outcomes of shunt surgery for iNPH, ranging from
24% to 96%,[33,34] with clinical improvement observed in 45%
of patients undergoing surgery at 1 year of follow‑up in the
1970s, improving to 81% in the studies published between
2006 and 2010.[35] With an improvement in understanding of
the iNPH disease process, improved and more appropriate
patient selection, and standardization of research approaches
over the past few decades, contemporary studies have shown
less variation and consistently reported favorable outcomes
ranging between 71% and 90%.[36‑38] The differences concerning
the different potential shunt types (e.g. ventriculoperitoneal,
lumboperitoneal, and ventriculoatrial) as specifically relating
to the previously described patient outcome measures have
not been adequately defined, and currently, no general
recommendation for a specific type of shunt to treat patients
with iNPH is possible. We, therefore, for the purpose of this
review, will use the term “CSF‑shunt procedure” to include all
treatment with any established potential CSF‑shunt types.[6‑9]
Short‑term Outcomes
As a provision, it is strongly recommended that practitioners
follow established guidelines to select patients with suspected
iNPH for consideration of treatment with a CSF shunt. As
a rule, failure to select patients based upon the identified
guidelines will result in a significantly lower positive response
to treatment with a CSF shunt. Other elements regarding
whether a patient can successfully tolerate surgery because of
medical comorbidities or frailty should also be considered.[6,7,9]
Following shunt surgery, improvement can be observed
in all the triad of iNPH symptoms[39] but at variable rates.
Of the iNPH triad, gait and balance are typically the most
 Isaacs and Hamilton: Outcomes for idiopathic normal pressure hydrocephalus
common and earliest symptoms of iNPH,[23,26] and the most
sensitive symptom to respond to shunting. Over 80% of
iNPH show improvement in gait and balance after surgery
and progressive improvement even years after the surgery.[40]
The pathophysiology of the gait impairment and subsequent
improvement with shunt surgery is not definitively established
but has been speculated to be in part related to a re‑expansion of
the midbrain locomotor regions and improvement in synaptic
activity.[41]
Cognitive difficulties are observed in up to 98% of iNPH
patients, tend to be gradual in onset, and are progressive but
may be subtle at initial presentation.[26,39,42] Significant cognitive
improvement is observed in over 80% of patients following
shunt surgery.[40] However, it is important to note that certain
aspects of cognition respond better than others.[43] For example,
among 47 iNPH patients who underwent shunt surgery,
over 80% demonstrated improvement in cognition on a variety
of neuropsychological tests. However, variable improvements
were observed in discrete domains of memory, inhibition,
learning, dexterity, speed, attention, and reaction times.[44]
Shunted patients exhibit improvement in their bladder
symptoms of urgency, frequency, and incontinence, with a
reported 30%–66% rate of recovery.[45‑48] The restoration of
blabber continence has been attributed in part to postoperative
reestablishment of blood flow and functional recovery of the
mid‑cingulate, which is normally responsible for inhibiting the
micturition complex.[49‑51]
In addition to improvements in the classic iNPH triad of
symptoms after treatment with a CSF shunt, improvements in
other psychiatric and behavioral symptoms that are prevalent
in the iNPH population have been reported. These symptoms,
such as lack of interest in activities, apathy, emotional blunting,
and hypersomnia, are often not evaluated in general clinical
practice or during clinical trials. However, in one report, among
429 iNPH patients who underwent shunt surgery, the daily
need for sleep improved from a median of 9 to 8 hours/day.[52]
In addition, significant improvement in geriatric depression
scale scores was reported in 176 iNPH who underwent shunted
surgery.[53]
Long‑term Outcomes
In general, approximately 90% of appropriately selected iNPH
patients who undergo CSF‑shunt treatment demonstrate
symptomatic relief in one or multiple domains of the clinical
iNPH triad on their immediate postoperative assessment.[21]
While several long‑term studies have demonstrated the clinical
improvements after shunting is long‑lasting and progressive,[40]
over the course of time, as the patients get older, some patients
plateau or decline in function.[19,21,38] Among 50 iNPH patients
who underwent surgery, 92% improved in the short term,
but after 10 years, 76% remained improved.[54] Similarly, in a
systematic review, the short‑term postoperative improvement
rates reported by studies between 2006 and 2010 was 81% at
3 months, which remained stable at 82% at 1 year but reduced to
73% beyond 3 years of follow‑up.[35] Therefore, when evaluating
the literature regarding iNPH patients’ CSF‑shunt treatment
outcomes, it is critical to identify short‑ versus long‑term
outcomes. When critiquing iNPH outcomes literature, it is
S564 Neurology India | Volume 69 | Supplement 2 | November-December 2021
essential to evaluate whether a report detailing a deterioration
in patient function has described the methodology that
systematically evaluated whether the clinical decline was
secondary to shunt malfunction before concluding that either
primary‑ or comorbidity‑related disease progression has
occurred. The latter information is not frequently provided and
represents a significant limitation for many studies.
An additional important element relevant to long‑term outcomes
corresponds to an identified survival benefit associated with
iNPH CSF‑shunt surgery. Among 979 patients in the Swedish
Hydrocephalus Quality Research, mortality was increased in
iNPH patients who did not improve in their gait and mRS scores
after surgery (hazard ratio 1.8), whereas those who improved
had a survival rate similar to the general population.[55]
Reports detailing long‑term outcomes associated with
CSF‑shunt treatment of iNPH describe variable response rates,
and it is important to examine potential reasons. For example,
in a retrospective review of 41 patients, Klassen et al. reported
a 50% drop in patients with improved gait at 1 year, with only
33%, 16%, and 13% with improvement in gait, continence, and
cognition, respectively, at 3 years.[56] Mirzayan et al.[57] reported
a 91% improvement in iNPH symptoms over a 7 year follow‑up
period. The variances in reported outcomes between Klassen
et al.[56] and Mirzayan et al.,[57] as well as among other studies, can
be attributed in part to differences in follow‑up durations and
stark differences in the outcome measures assessed, the scales
used to measure outcomes, and the statistical methodology used
to analyze outcome data. Another important factor that impacts
variability in reported outcomes is the age of category of adults
been assessed. In 482 iNPH patients, Takeuchi et al. showed
that while 93% of patients demonstrated early improvement in
iNPH scale scores after surgery, an age differential developed
when looking at long‑term outcomes. After 4 years of follow‑up,
Takeuchi et al.[58] found that 82% of those less than 80 years of
age at the time remained improved, while only 70% of patients
above the age of 80 years old showed improvement.
High rates of reported shunt failure leading to surgical shunt
revision will have an obvious significant impact on iNPH
outcomes. However, there is heterogeneity in what constitutes
a definition of shunt failure in the literature due to the lack of
best‑practice guidelines to direct the diagnostic evaluation of
a suspected shunt failure, with shunt revision rates ranging
from approximately 16% to 53%.[35,40] It is important to again
emphasize that when critiquing iNPH outcomes literature, it
is necessary to assess whether the study methodology includes
a systematic evaluation to determine if the clinical decline
was secondary to shunt malfunction before concluding that
a primary‑ or comorbidity‑disease related progression had
occurred. Given that postoperative improvement in iNPH is
expected to be long‑lasting,[40] failure to respond to or worsening
of symptoms after shunt surgery should prompt investigations
for a possible shunt malfunction. It is reassuring that patients
who undergo shunt revisions continue to benefit from shunt
surgery, with approximately 70% long‑term improvement.[40]
Outcomes Associated with Delayed Treatment
Delayed treatment of iNPH has been shown to lead to worsening
symptoms that eventually become irreversible.[59,60] While there
 Isaacs and Hamilton: Outcomes for idiopathic normal pressure hydrocephalus
is evidence to suggest that longer duration of preoperative
symptoms is associated with decreased postoperative
improvements, [61] there are only a few studies that have
reported the outcomes of iNPH when treatment is significantly
delayed. In a prospective study of 33 iNPH patients where
the surgery for four patients was delayed by 34 months due
to logistical issues, 10 patients declined surgery, and all the
patients who did not undergo surgery had global decline
in their gait, balance, and cognitive assessments.[62] In an
open‑label randomized trial of 93 patients, delaying surgery by
3 months was associated with poorer short‑term outcomes after
surgery when compared to patients who underwent surgery
within 1 month of iNPH diagnosis.[59] In a recent study on 102
iNPH patients, 33 patients whose surgery was inadvertently
delayed by a median of 13 months not only experienced a
worsening of their iNPH symptoms but also their 4‑year
mortality rate was 39%, a 2.6  times risk of death  (adjusted
hazard ratio) compared to the patients who had no delays in
their treatment.[63]
Outcomes of Untreated iNPH
A final consideration relates to the potential issues of symptom
progression and the likely probability of worse clinical
outcomes that may cause a delay or failure to refer patients for
assessment and treatment. The average duration of symptoms
identified by most studies at the time of initial assessment is
approximately 2 years. There is evidence that asymptomatic
ventriculomegaly typically precedes the development of
clinical symptoms in iNPH, with some longitudinal studies
demonstrating that iNPH symptoms are preceded by a
4‑ to 8‑year period of asymptomatic progressive ventricular
dilatation.[26] While the onset of the symptoms is typically
insidious, they gradually progress with increasing magnitude
of irreversibility if not promptly treated. In the short term,
patients with iNPH who undergo treatment prior to the
development of irreversible symptoms demonstrate the best
improvements.
Several studies have reported on the natural history of patients
with untreated iNPH. While spontaneous but marginal
improvements  (or fluctuations) in the short term have been
reported, it is often followed by progressive worsening of
symptoms.[64,65] Untreated iNPH is associated with significant
morbidity and increased mortality. In a randomized controlled
trial of lumboperitoneal shunt‑treated versus untreated iNPH
patients (SINPHONI‑2), only 5% of the untreated group
compared with >80% of the treated group showed clinical
improvement at 1 year.[59] In a population study comparing
1180 individuals without iNPH to a group of 24 iNPH patients,
patients with untreated iNPH had a much lower survival with
a 5‑year mortality risk of >80% and an adjusted hazard ratio of
3.8 for death.[66] The morbidity and mortality associated with
untreated iNPH is often due to increased risk of falls, loss of
the ability to mobilize independently, and malnutrition.
HRQoL Outcomes
While the objective outcomes of CSF‑shunt treatment of
adult patients with hydrocephalus are important, it is equally
important to consider the subjective outcomes from the
patient’s perspective. Among 623 respondents from a group
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S565
of 979 treated iNPH patients that were contacted to describe
their outcomes through questionnaires on a regular basis,
75% reported they were feeling better at 3 months of their
surgery than they were preoperatively, and approximately
69% reported that they were still feeling better or unchanged
6 years after surgery.[67]
There is growing interest in utilizing HRQoL tools to assess
patient outcomes in medicine. HRQoL measures focus on
patient‑reported patient‑centered outcomes to evaluate the
impact of their perceived health on their physical, mental,
emotional, and social well‑being and overall QoL.[68] Thus,
HRQoLs provide a comprehensive evaluation of treatment
outcomes that may otherwise not be identified by standard
clinical outcomes. HRQoLs data are typically obtained through
patient questionnaires that may be generic, such as the Health
Utilities Index Mark,[69] or tailored to a specific condition, such
as the Hydrocephalus Outcome Questionnaire, which has been
used in the pediatric hydrocephalus population.[70]
In adult hydrocephalus, there have only been a few
published studies that have focused on HRQoL, and
most have used generic measures such as the EuroQoL
5 Dimensions (EQ5D) [71] and the 15D. The EQ5D is a
comprehensive questionnaire that assesses HRQoL in five
domains: mobility, self‑care, usual activities, pain/discomfort,
and anxiety/depression. Patients are also able to score their
overall perceived HRQoL on a visual analog scale between 0
and 100. Of 37 iNPH patients assessed with the EQ5D before
and after surgery, 86% reported improvements in the HRQoL,
with scores like those of the general population.[72] Israelsson
et al.[73] recently examined 176 iNPH patients, demonstrating
that while treatment with a CSF‑shunt shunted resulted in a
significant improvement in HRQoL, these patients still have
lower HRQoL than matched controls. Furthermore, the QoL
scores remained improved on EQ5D measures when assessed
at approximately 21 months after surgery. Symptoms of
depression and severity of gait disturbance were found to be
the strongest predictors of low HRQoL scores in the patients
with iNPH.[73] Finally, the HRQoL reports of iNPH patients do
demonstrate some variability. For example, utilizing the 15D
HRQoL scale, Junkkari et al.[74] showed that among 132 iNPH
patients, only 43% reported improvement in their QoL after
1 year despite favorable postoperative clinical disease‑specific
responses. The lack of HRQoL improvement in the majority
of the patients were attributable to patient characteristics
such as frailty and preexisting comorbidities. Furthermore,
it is important to evaluate whether a deterioration in patient
function was secondary to shunt malfunction before concluding
that primary‑ or comorbidity‑disease‑related progression has
occurred.
Conclusion
As a proviso, it is strongly recommended that practitioners
follow established guidelines to select patients with suspected
iNPH for consideration of treatment with a CSF shunt. As
a rule, failure to select patients based upon the identified
guidelines will result in a significantly lower positive response
to treatment with a CSF shunt. Objective measures of gait,
balance, and cognition are recommended. If iNPH scales are
used to describe patient outcomes, it is recommended that the
 Isaacs and Hamilton: Outcomes for idiopathic normal pressure hydrocephalus
actual objective values also be included as part of the reporting
process. Other patient‑specific issues not reviewed here, such
as medical comorbidities or frailty, may also influence the
surgical selection process.
Over  90% of appropriately identified iNPH patients who
undergo CSF‑shunt treatment demonstrate symptomatic relief
after surgery, and long‑term studies have shown that in the
majority of patients, the clinical improvements are long‑lasting,
with over 70% demonstrating improvement longer than 6 years
after treatment. The surgical treatment of iNPH with CSF‑shunt
surgery has an overall low risk of morbidity and mortality.
However, the course of treated iNPH is often confounded
by the age‑ and comorbidity‑related decline in health, and as
patients progress in age, the improvements may plateau or
decline. Nevertheless, this must be placed in context. Delaying
surgical treatment for iNPH is detrimental to patients. Patients
who are untreated have a high risk of morbidity and mortality
compared with those who undergo CSF‑shunt surgery.
In addition to objective measures of outcomes focused on gait
and cognition, it is equally important to assess patient‑centered
subjective measures of HRQoL as there can be a concerning
disconnect between the clinician and patient measured
outcomes. There is a need for standardized measures of
outcomes validated by adequately powered studies by using
consistent HRQoL scales to provide the most accurate estimates
in adult hydrocephalus patients.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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 Review Article
Access this article online
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Website:
www.neurologyindia.com
DOI:
10.4103/0028-3886.332251
Department of
Neurological Sciences,
Christian Medical
College, Vellore,
Tamil Nadu, India
Address for
correspondence:
Dr. Vedantam Rajshekhar
Department of
Neurological Sciences,
Christian Medical
College, Vellore,
Tamil Nadu ‑ 632 004,
India.
E‑mail: rajshekhar@
cmcvellore.ac.in
© 2021 Neurology India, Neurological Society of India | Published by Wolters Kluwer - Medknow S569
Three Decades of Vellore Grading
for Tuberculous Meningitis with
Hydrocephalus: A Reappraisal
Vedantam Rajshekhar
Abstract:
Background: This review documents the evolution of the Vellore grading system for tuberculous meningitis
and hydrocephalus (TBMH), its evaluation by different authors, and analyzes the need for further modification
in light of the published literature.
Methods: Published literature was searched in PubMed and Google Scholar using the search terms,
“tuberculous meningitis hydrocephalus” and “Vellore grading.” The retrieved articles were reviewed by the
author and the appropriate ones were chosen for inclusion in the study.
Results: Vellore grade (1–4, with 1 being the best grade and 4 being the worst grade) was found to be the
sole statistically significant factor associated with outcome following VP shunt or ETV in several studies.
Additionally, Vellore grades also correlate with the likelihood of success following ETV. However, the use of
response to external ventricular drainage (EVD) in managing Vellore grade 4 patients has remained contentious
as a small but significant proportion of patients have a good outcome following shunt, irrespective of their
response to the EVD. The latter findings suggest that grade 4 patients might not constitute a homogenous
group. It is proposed that grade 4 be subdivided into grades 4a and 4b, which might help in prognostication
and in surgical management of the hydrocephalus in patients with TBMH.
Conclusions: Vellore grading has proved its utility as a prognostic tool and can aid surgical decision‑making.
However, management of patients in grade 4 might be better rationalized with its division into grades 4a
and 4b.
Key Words:
Endoscopic third ventriculostomy, outcome, prognosis, shunt surgery, tuberculous meningitis
Key Message:
Vellore grading for patients with TBMH has been found to be a reliable tool to prognosticate outcomes
following shunt or ETV. However, subcategorization of grade 4 into grades 4a and 4b might rationalize the
management of patients in this grade.
C linicians in India and several other
impoverished regions of the world continue
to see several patients with tuberculous
were made to correlate the preoperative grade
with the outcome following shunt surgery. The
variable response of patients with TBMH to
meningitis (TBM). One of the most common shunt surgery makes it important to grade the
complications of TBM is hydrocephalus (TBMH), severity of TBM to prognosticate the surgical
this complication being commoner in outcome.
children.[1] Bhagwati, in 1971, first proposed the
use of ventriculoatrial (VA) shunts to manage This article documents the history of grading
the hydrocephalus in patients with TBMH. [2] of patients with TBMH with a focus on the
Although the reported outcomes following shunt development of Vellore grading and its
surgery in the series reported in the 1970s and utilization. The article also discusses the possible
1980s were variable, good outcomes were noted need for further changes to the Vellore grading
in approximately 60% of patients on average.[2‑8] based on recent reports of outcomes in patients
The authors of some of these series graded undergoing surgery for TBMH.
the severity of the TBM in their patients prior
to shunt surgery, but no significant attempts
How to cite this article: Rajshekhar V. Three
This is an open access journal, and articles are distributed under the terms Decades of Vellore Grading for Tuberculous Meningitis
of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 with Hydrocephalus: A Reappraisal. Neurol India
License, which allows others to remix, tweak, and build upon the work 2021;69:S569-74.
non‑commercially, as long as appropriate credit is given and the new
creations are licensed under the identical terms. Submitted: 05‑May‑2021   Revised: 09-Sep-2021
Accepted: 13-Sep-2021   Published: 11-Dec-2021
For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com
 Rajshekhar: Vellore grading for TBMH

Methods outside the authors’ institution. A modification of this grading

PubMed and Google Scholar were searched using the terms
“tuberculous meningitis hydrocephalus” and “Vellore
grading.” PubMed search yielded only five articles, whereas
the Google Scholar search yielded 168 articles. The titles and
abstracts of these articles were read and the relevant articles
were chosen for a detailed review. Several articles from the
Google Scholar search were found to be irrelevant. Finally,
there were 13 articles that used Vellore grading while reporting
outcomes in patients with TBMH who had undergone CSF
diversion, and three review articles that reported on the use
of Vellore grading in patients with TBMH. Other articles not
revealed in the search of these two databases were obtained
through cross‑references of the relevant articles or from the
personal knowledge of the author.
Early grading systems
The grading system proposed by the Medical Research
Council (MRC) of the United Kingdom in 1948 is the one
most frequently used to grade patients with TBM [Table 1].[9,10]
Lincoln et al.,[11] in 1960, introduced a grading system for
TBM in children, which again had three grades but differed
considerably from the MRC grading [Table 1]. For several years,
these were the only grading systems available for TBM. In 1977,
Bhagwati and Singhal[12] proposed a grading system for TBM
that had five grades [Table 1]. However, this grading system
did not gain popularity and was only ever used in another
article published by them in 1982.[5]
Evolution of the Vellore grading system
Although the Vellore grading system for TBMH was formally
published in a peer‑reviewed publication in 1991; its origins date
back to 1974. In 1974, Reddy et al.[13] from Vellore first proposed
a simple grading system for TBMH with four grades [Table 1].
The grading was proposed only for patients with TBM with
altered sensorium; those with normal sensorium were not
graded by this system. In their study of 61 patients with TBMH
who underwent VA shunt or ventriculoperitoneal (VP) shunt,
32 had normal sensorium and 29 had altered sensorium. Of
those with altered sensorium, 36.8% in grades I and II (better
grades) died on follow‑up, whereas 70% of those in the worse
grades (III and IV) died. The grading system was not published
in a peer‑reviewed journal and hence it remained unknown
system was used to study the long‑term outcome in patients
with TBMH who had undergone shunt surgery. This study,
published in 1991, had the first version of what was later labeled
the Vellore grading system.[14] Some authors who used this
grading system also referred to it as the “Palur” grading system
after the first author of that publication. We prefer the term
“Vellore grading system” as the framework for this grading
system was taken from work done earlier in the department.
Vellore grading (1991)
To address the lack of a validated grading system that had been
used for prognostication in patients with TBMH, we evolved
the Vellore grading system [Table 2]. The system was proposed
in a retrospective study of 114 patients with TBMH, all of whom
had undergone VA or VP shunts and who were followed
up for 6 months to 13 years (mean: 45.6 months).[14] The first
two grades were applied to patients with normal sensorium,
whereas the last two grades had patients with varying degrees
of altered sensorium. The grading system was designed to
be applied to patients in a retrospective study wherein the
preoperative clinical data were gathered from hospital records.
Based on the follow‑up outcome, we proposed a management
algorithm for patients in different grades.[14] Essentially, the
algorithm advised early shunting for patients in grades I and
II whereas those in grades III and IV should be chosen for
shunt surgery on the basis of their response to two to three
days of external ventricular drainage (EVD) of CSF. Those who
improved should go on to have shunt surgery whereas those
who did not improve should receive the best medical therapy.
Modified Vellore grading (1997)
Although the Vellore grading of 1991 was found to be useful for
decision making and prognostication of patients with TBMH,
it suffered from the possibility of interobserver variability in
the grading of patients as the patient assessment was subjective
to a large extent. To overcome this limitation, we modified
the grading by incorporating the Glasgow Coma Scale score
in the grading [Table  2]. The modified grading system was
published as part of a prospective study of outcomes in
poor‑grade (grades 3 and 4) TBMH patients.[15] Patients in
grades 1 and 2 had a GCS score of 15, patients in grade 3 had a
GCS score of 9–14, and those in grade 4 had a GCS score of 3–8.

Table 1: Commonly used grading/staging systems for patients with tuberculous meningitis (TBM) and
tuberculous meningitis with hydrocephalus (TBMH)
Grade/ Medical Research Lincoln et al., 1960 Reddy et al., 1974* Bhagwati and Singhal, 1975 Modified MRC
Stage Council (MRC), 1948 staging, 2005
1 Fully conscious, no Meningitis with no When the patient Only systemic symptoms and signs GCS 15
paresis neurological involvement was arousable and such as pyrexia, headache, etc., without
answering questions overt meningeal signs
2 Decreased level of Evidence of neurological Arousable, but not Presence of overt meningeal signs such GCS 10‑14 or 15
consciousness, localizing changes with no marked answering questions as neck stiffness etc. with neurological
pain changes in sensorium deficits
3 Deeply comatose±gross Marked neurological and Responding to pain Conscious but with a neurological GCS ≤10
paresis sensorial changes only deficit such as cranial nerve palsies and
hemiparesis
4 Comatose and not Stuporous to semiconscious, with or
responding to pain without focal neurological deficit.
5 Decerebrate or deeply comatose state.
*Grading was only used for patients with altered sensorium.

S570 Neurology India | Volume 69 | Supplement 2 | November-December 2021

 Rajshekhar: Vellore grading for TBMH
Table  2: Vellore and modified Vellore grading
systems
Grading system Grading
Vellore grading, Grade I
1991 (Palur 1. headache, vomiting, fever, and/or neck stiffness
et al.) 2. no neurological deficit
3. normal sensorium
Grade II
1. normal sensorium
2. neurological deficit present
Grade III
1. altered sensorium but easily arousable
2. dense neurological deficit may or may not be
present
Grade IV
l. deeply comatose
2. decerebrate or decorticate posturing
Modified Vellore Grade 1: GCS 15; no deficits
grading, 1998 Grade 2: GCS 15; neurological deficits present
(Mathew et al.) Grade 3: GCS 9‑4; neurological deficits may or
may not be present
Grade 4: GCS 3‑8; neurological deficits may or
may not be present
The use of GCS made the grading reliable and reproducible and
minimized the chances of interobserver variability. The grading
also used Arabic numerals, in contrast to Roman numerals used
in the original Vellore grading. For the sake of uniformity, all
Vellore grades  (original or modified) will be represented in
Arabic numerals from hereon.
Comparison with other grading systems
All the grading systems for TBM prior to the introduction of the
modified Vellore grading system were essentially subjective.
The Lincoln system was the most subjective of all, with no
clear definitions of terms such as “neurological involvement,”
“marked changes in sensorium,” or “sensorial changes.” The
original Vellore grading also had similar shortcomings. “Easily
arousable,” which was a feature of Vellore grade 3 patients, is
open to different interpretations. The MRC grade I excludes
patients with “paresis”; therefore, if a patient has no alteration
of sensorium but has paresis present, then it is not possible to
categorize such a patient using the MRC system.
The other major deficiency of the MRC and Lincoln grading
systems was that they had only three grades. Stage II of the
MRC system and Stages II and III of the Lincoln system
encompass a wide range of clinical situations with varying
degrees of alteration of sensorium. Understandably, there
would be significant heterogeneity in patients categorized in
these stages. Although the MRC staging was modified in 2005
to include the GCS score, it still has only three grades.[10] It
addressed one of the problems with the original MRC staging,
wherein patients with normal sensorium with neurological
deficits could not be categorized. In the modified MRC staging,
patients with GCS 15/15 with neurological deficit were
categorized as MRC stage 2.[10] However, Stage 3 of the MRC
grading includes patients with GCS scores of 3–10. This is a
very wide range of GCS scores and therefore does not constitute
a homogeneous group for prognostication. By having four
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S571
grades, the modified Vellore grading system enables patients
with TBM and TBMH to be stratified into more homogeneous
groups. This prevents too much variation in the prognosis of
individual patients in a particular grade.
Clinical utility of the Vellore grading system
The Vellore grading system was proposed both as a prognostic
tool and to decide on the benefit of shunt surgery in patients
in different grades.
i. Prognostic value
In the initial 1991 retrospective study, mortality rates
for patients in the different Vellore grades at long‑term
follow up were as follows: grade 1, 20%; grade 2, 34.7%;
grade 3, 51.9%; and grade 4, 100% (P < 0.001).[14] In the
prospective study, using the modified Vellore grade, this
clear separation of mortality rates for the different grades
was confirmed  (P = 0.002), although the follow‑up was
shorter than the retrospective study (mean: 23.1 months vs.
45.6 months).[15] It should be noted that the prognostic value
of the grading was verified in patients with an average
follow‑up of over 2–4 years.
Several studies from all over India and other countries have
validated the prognostic value of the Vellore and modified
Vellore grading in TBMH patients who underwent shunt
surgery or ETV [Table 3].[16‑24]
ii. Decision regarding surgery
The extremely poor outcome in patients in Vellore grade 4
led us to question the policy of universal shunting in this
group of patients. It seemed that raised intracranial pressure
due to the hydrocephalus was not a significant cause of the
altered sensorium in most of these patients. The altered
sensorium was possibly due to a combination of severe
meningoencephalitis and ischemia of the basal ganglia,
diencephalic structures, and midbrain. We suggested
that patients in this group who would benefit from shunt
surgery should be chosen based on their response to a
period of external ventricular drainage (EVD).[14] EVD was
also suggested as an option for patients in Vellore grade III,
but the prospective study[15] showed that response to EVD
did not correspond to outcome in patients in this grade;
hence, we do not recommend EVD for these patients except
if the patients are unfit for general anesthesia due to their
nutritional status or other factors.
We suggest prompt surgery for patients in Vellore and
modified Vellore grades 1 and 2 and possibly 3 as the
prognosis on long‑term follow‑up is good in over 80%–
90% of patients in grade 1 and approximately 30% in
grade 3 patients.[25,26]
iii. Predictor of success of ETV
The ability to predict the success of ETV using the Vellore
grade has been shown by some authors.[18,20,22] Goyal et al.[22]
and Yadav et al.[20] found that the ETV was successful in
100% of patients in Grade 1, whereas the success rate was
33% to 50% in Vellore grade 4 patients. Possibly, the thicker
basal exudates and thicker third ventricular floor due to the
ependymitis, which are more likely to be associated with
grade 4 disease, might be the factors that lead to higher
failure rates for ETV.
Management of Vellore grade 4 patients
Several authors have supported the use of response to EVD to
choose patients in Vellore grade 4 for shunt surgery.[14,15,17,19] In a
 Rajshekhar: Vellore grading for TBMH

Table 3: Validation of Vellore grading for TBMH

Authors, year, type of surgery Number of patients in different grades Improvement/Survival (%) Comments
Palur et al., 1991 114, C+A Grade 1: 80
Shunt Grade 1: 5 Grade 2: 65.3
Grade 2: 75 Grade 3: 48.1
Grade 3: 27 Grade 4: 0
Grade 4: 7
Singh and Kumar, 1996 140, C Grades 1 and 2: 100
Shunt Grade 1 and 2: 7 Grade 3: 60.3
Grade 3: 46 Grade 4: 34.5
Grade 4: 87
Mathew et al., 1998 30, C+A Grade 3: 66.7
Shunt Grade 3‑18 Grade 4: 8.3
Grade 4‑12
Agrawal et al., 2005 37, C Grade 2: 62
Shunt Grade 2: 16 Grade 3: 40
Grade 3: 15 Grade 4: 0
Grade 4: 6
Jha et al., 2007 14, A+C ETV failed in all grade 4 patients
ETV Grade 2: 2
Grade 3: 8
Grade 4: 4
Sil and Chatterjee, 2008 32, C Patients in Grade 2 had better outcome than those in Grade
Shunt Grade 2: 20 3.
Grade 3: 12
Yadav et al., 2011 59; 39 C, 20 A Grade 1: 95.2
ETV Grade 1:21 Grade 2: 88.9
Grade 2: 27 Grade 3: 57
Grade 3: 7 Grade 4: 50
Grade 4: 4 Vellore grade was the only significant prognostic factor for
survival on linear regression analysis (P=0.001)
Savardekar et al., 2013 26, C Grade 3: 71.4
Shunt Grade 3: 21 Grade 4: 20
Grade 4: 5
Goyal et al., 2014 24, C Grade 3: 70.9
Shunt/ETV ‑ RCT Mean grade: 3.1 Grade 4: 0
ETV success was related to the Vellore grade
Grade 1: 100%
Grade 4: 33.3%
Aranha et al., 2018 26, C Modified Vellore grade was the only factor associated
Shunt/ETV ‑ RCT Grades 1 and 2: 36 significantly with outcome in both shunt and ETV
Grades 3 and 4: 16 groups (Odds ratio: 4.2)
Harrichandpershad et al., 2019 15, A Grade 1: 100
HIV positive Grade 1: 3 Grade 3: 66.7
Shunt Grade 3: 12 Patients in grade 4 should undergo a trial of external
ventricular drainage and only those who improve should
undergo a definitive procedure
C, children; A, adults; ETV, endoscopic third ventriculostomy; RCT, randomized controlled trial.

recent publication from South Africa in 2019 on the outcome of
HIV‑positive patients with TBMH, the authors recommended
that patients in grade 4 should only be shunted if they improve
with a trial of EVD.[24] They conclude that this approach will
allow for the optimal utilization of precious resources.
However, this approach has been challenged by others
who suggest that a nihilistic approach to these patients is
unwarranted and all patients with TBMH in grade 4 should
undergo shunt surgery. The first such report published in 2009
studied the outcome in 95 patients with grade 4 TBMH.[27]
They evaluated whether the response to EVD predicts the
outcome following shunt surgery in grade 4 TBMH patients.
Although the authors mention that 43 patients received an
EVD prior to shunt, the flow chart in their article suggests that
in some patients, only a ventricular tap was performed and
drainage was not done. It is obvious that sensorium, which
does not improve following a ventricular tap, might do so after
2–3 days of EVD. Besides this discrepancy, they lost 55 patients
to follow‑up. Of the 40 patients available for follow‑up for

S572 Neurology India | Volume 69 | Supplement 2 | November-December 2021

 Rajshekhar: Vellore grading for TBMH
a median duration of 12 months, nine had died in hospital.
Therefore, follow‑up was only performed in 31 patients; 18 of
them had a good outcome or moderate disability (GOS 4 and 5).
The authors did not comment on their finding that patients who
improved following EVD had better outcome than those who
did not. EVD/ventricular tap was performed in 19 followed‑up
patients. Of these, eight had improved to Grades 2 or 3 prior
to shunt and three (38%) had GOS 4 or 5 outcome. Of the 11
who did not improve, only two (18%) had the same outcome
scores (GOS 4 or 5) at follow‑up. Although these numbers are
too small to analyze for statistical significance, they indicate
that improvement with EVD is probably associated with
better outcomes with shunt. Finally, of the 21 patients who
underwent direct VP shunt without EVD, 13 (62%) improved
to GOS 4 or 5 at follow‑up. Therefore, patients in the direct VP
shunt group seem to have had a significantly better outcome
than those who underwent EVD (P = 0.03; Fisher’s exact test).
This difference was not analyzed or commented upon by the
authors. Furthermore, they did not include this as a prognostic
factor in the multivariate analysis. Finally, a good outcome in
62% of grade 4 TBMH patients following shunt surgery has
been reported in only one other publication from China that
included 19 grade 4 patients.[28]
Authors who oppose the use of response to EVD to select
patients for shunt surgery cite the following reasons: (i)
improvement in sensorium following drainage of CSF might
not occur for several days and hence evaluating the response
to EVD after 2 or 3 days of drainage can be misleading; (ii)
EVDs are prone to get infected and are therefore impractical;
and (iii) some evidence suggests that response to EVD does not
predict outcome following shunt.[21,27,28] Those who support the
use of EVD argue that (i) universal shunting of these patients
is an inappropriate use of limited resources given the high
mortality and morbidity in these patients; (ii) children with
low ventricular pressure do not have improvement following
shunt; and (iii) use of response to EVD allows surgeons to select
patients who are likely to benefit from shunt surgery.[14,15,17,19,24]
Notwithstanding the shortcomings in the data presented by
those who argue for universal shunting, there seems to be some
merit in considering direct shunt in selected patients in grade 4.
Subcategorization of Vellore grade 4 patients
Patients in Vellore grade 4 have a GCS score that ranges from
3 to 8. The above discussion indicates these patients might
not constitute a homogeneous group for prognostic and
management purposes and need further division. A recent
systematic review on the outcome in patients with TBMH
following VP shunt surgery also suggested the need for a
“predictive model” for choosing patients in Vellore grade 4
who might benefit from shunt surgery.[29] Subcategorization
of patients in grade 4 is an effort in that direction.
Several authors have shown that TBMH and TBM patients
with GCS of 3–5 or 3–6 and those with basal ganglia and brain
stem infarcts have an extremely poor prognosis with high
mortality rates.[27,30‑33] We reported that 8 of 16 (50%) patients
in Vellore grades 3 and 4 who died in our prospective study
of TBMH had brain stem infarcts.[15] Hydrocephalus in most
patients with GCS of 3–6 and in those with basal ganglia and
brain stem infarcts might not contribute significantly to the
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S573
Table  4: Suggested changes to modified Vellore
grading
Grade Description
Grade 1 GCS 15; no neurological deficit
Grade 2 GCS 15; neurological deficit is present
Grade 3 GCS 9‑14; neurological deficit may or may not be present
Grade 4a GCS 7, 8; no basal ganglia or brain stem infarcts on
neuroimaging
Grade 4b GCS 7, 8; basal ganglia or brain stem infarcts present on
neuroimaging Or GCS 3‑6
altered sensorium. Even those who support universal shunt
surgery in grade 4 patients urge caution in performing shunts
indiscriminately in this group of patients.[27] Based on the
observations of these authors and our experience,[15,27,30‑32] we
propose the creation of subgrades 4a and 4b [Table 4].
Patients in grade 4a can be offered direct shunt surgery
without determining a response to EVD. In contrast, patients
in grade 4b are those in whom the prognosis is extremely poor
and response to EVD should be used to choose patients for
shunt surgery. While it would be intuitive to use the duration of
altered sensorium (<2 weeks) as an additional factor to decide
whether to operate a grade 4b patient, it has not been found to
be associated with outcome following shunt or ETV.[22]
Conclusions
Since its introduction nearly three decades ago, Vellore grading
for patients with TBMH and its modified version have been
validated in many studies for their reliability, prognostic value
for outcome after shunt surgery, and utility in predicting the
success of ETV. With the available evidence that patients in a
subgroup of grade 4 have significantly poorer outcomes than
others in the same grade, it might be justified to have two
subcategories in this grade. Validation of this subcategorization
is required in further studies.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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 Review Article

Access this article online

Quick Response Code:
Controversies in Hydrocephalus: QUO
VADIS
Suhas Udayakumaran, Jogi V Pattisapu1

Website: Abstract:
www.neurologyindia.com
Background: Hydrocephalus is a complex issue characterized by increased intracranial pressure secondary
DOI: to obstruction of cerebrospinal fluid flow and occasionally due to overproduction. As a result, the entity has
10.4103/0028-3886.332269 challenges of different dimensions at the level of understanding and management.
Methods: A  literature search, systematic review, and meta‑analysis of eligible studies were conducted
in the major databases. The literature review included relevant articles on hydrocephalus published until
June 1, 2021  (no starting date), databases being the only limitation considering the broadness of the
subthemes. Controversies themes were chosen among the literature, not including treatment dilemmas
and hydrocephalus research. The further detailed search included these selected themes and an updated
literature review on the subjects.
Results and Discussion: Controversies are a hallmark of incomplete science; most complex concepts harbor
several debates at various levels. This article reviews controversies in hydrocephalus, offering some updates
on popular discussions. It is not meant to be an exposition of the topics themselves but to collect the status
quo of unresolved concepts in hydrocephalus.
Conclusions: As with most chronic and complex disorders, hydrocephalus welcomes controversy as a healthy
discussion platform to exist until we understand the disorder to its minutest.
Key Words:
Controversy, dilemma, metaanalysis, updates

Key Message:
As with most chronic and complex disorders, hydrocephalus welcomes controversy as a healthy discussion
platform to exist until we understand the disorder to its minutest.

”E mbrace controversy. It gives you a platform.

Department of
Neurosurgery,
Division of Paediatric
Neurosurgery, Amrita
Institute of Medical
Sciences and Research
Centre, Kochi, Kerala,
India, 1Pediatric
Neurosurgery,
University of Central
Florida College of
Medicine, Orlando
Florida, US
Address for
correspondence:
Dr. Suhas Udayakumaran,
Division of Paediatric
Neurosurgery, Department
of Neurosurgery, Amrita
Institute Of Medical
Sciences and Research
Centre, Kochi ‑ 682 041,
Kerala, India.
E‑mail: dr.suhas@gmail.
com
It is a teacher, a clarifier, and your friend,
especially if you are trying to make a change.”
~ Gloria Feldt
Hydrocephalus is a complex issue characterized
by increased intracranial pressure (ICP) secondary
to obstruction of cerebrospinal fluid (CSF) flow
and occasionally due to overproduction. As
a result, the entity has challenges of different
dimensions at the level of understanding and
management.
Controversies are a hallmark of incomplete
science. Most complex themes have controversies
at various levels. This article reviews controversies
in hydrocephalus and provides an update
on the same. The report is not meant to be an
exposition of the topic themselves but to collect
the status quo of the controversial subjects in
This is an open access journal, and articles are distributed under the terms
of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0
License, which allows others to remix, tweak, and build upon the work
non‑commercially, as long as appropriate credit is given and the new
creations are licensed under the identical terms.
For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com
hydrocephalus. Additionally, the topics in this
article have been reviewed in detail by other
authors, and we offer a compilation of “sparks”
for future endeavors dealing with the challenges
of hydrocephalus.
Methods
A literature search, systematic review, and
meta‑analysis of eligible studies were conducted in
the major databases (PubMed, EMBASE, Medline,
Cochrane Library, TRIP database, CINAHL, and
Google Scholar), using the MeSH or free text
terms and eligible articles. The literature review
included relevant articles on hydrocephalus
published until June 1, 2021 (no starting date),
databases being the only limitation considering
the broadness of subthemes. In addition, the
reference lists of all the included studies were also
reviewed for additional eligible articles.
How to cite this article: Udayakumaran S,
Pattisapu JV. Controversies in Hydrocephalus: QUO
VADIS. Neurol India 2021;69:S575-82.
Submitted: 29‑Jun‑2021 Accepted: 18-Sep-2021
Published: 11-Dec-2021

© 2021 Neurology India, Neurological Society of India | Published by Wolters Kluwer - Medknow S575
 Udayakumaran and Pattisapu: Controversies in hydrocephalus

Controversies themes were chosen among the literature, not

including treatment dilemmas and hydrocephalus research
[Figure 1]. The further detailed search included these selected
themes and an updated literature review on the subjects.

Results

Conceptual controversies
a. Definition and classification
b. The CSF Flow
c. “Normal” ICP in infancy and the selection of optimal
valve pressure.

Definition and classification

Hydrocephalus is not a single pathological entity but a
pathophysiological condition of disturbance in CSF dynamics;
hence, the definition and classification of hydrocephalus are
crucial, offering a most complicated academic challenge.
Hydrocephalus classification is often confusing and complex,
prompting many authors to offer various options. Historically,
two significant descriptions of major pathways and altered
CSF dynamics or circulation were adopted. These are
“communicating vs non‑communicating” by Dandy in 1919[1]
and “non‑obstructive vs obstructive” by Russel.[2]
Dandy and his pediatrician colleague, Blackfan, performed
ventricular punctures, injected supravital dyes into ventricles
and later performed lumbar punctures with these tools. If the
dye was recovered in the spinal tap, the hydrocephalus was
classified as “communicating.” If no dye was retrieved in the
lumbar theca, the hydrocephalus was considered “obstructive”
or “non‑communicating.” Based on the same concept, Ransohoff
proposed classification into intraventricular obstructive and
extraventricular obstructive hydrocephalus.[3] Rekate proposed
a point of obstruction based primary classification.[4,5] The
primary classification of point of obstruction was postulated
to be modified by the etiology of the inciting condition, the
chronicity or rapidity of onset, and the person or experimental
animal.[4] Further, he could demonstrate utility based on the
classification.[4]
Areas of agreement: Hydrocephalus is a pathophysiological
condition with disturbance of CSF dynamics secondary to
varying etiology and dynamics. The basic tenet of obstructive
and communicating hydrocephalus is acceptable in the
broadest sense of disturbed pathophysiology.
Figure 1: Controversy overlaps with other tenets of science. Clinical controversy
is the harbinger and precursor of the concepts of tomorrow, simultaneously dealing
with clinical dilemmas. Amid these entities originates research that powers science
forward. Thus, controversies are earliest in the timeline of scientific progress and
the seeds of future research. Controversy:, clinical dilemmas and future research:
A Moving Continuum
The CSF flow
We do not yet have a widely accepted and perfected hydrocephalus
theory. CSF physiology should not be considered as a
unidirectional flow through a unique anatomical well‑defined
pathway. More likely, it is a complex and dynamic equilibrium of
fluids between vascular, neural, and cisternal spaces. In addition,
the neurovascular interface is involved in CSF production and
resorption. This activity seems to be driven by hydrostatic and
osmotic forces, avoiding de facto the necessity of a real flow as
classically described.[11] Researchers have since developed an
alternative hydrodynamic model that explains hydrocephalus
as a disorder of intracranial pulsations.[12‑15] Substantial animal
and human evidence have emerged, supporting the critical role
of the glymphatic system in animal and human physiology.[16‑18]
Areas of agreement: At the one end of the glymphatic system,
there is now relative agreement regarding the dual contribution
of the arachnoid granulations and the cranial/spinal nerves in
CSF clearance.
Despite this, there is a widespread lack of understanding of
how these two components interact with each other at various
ages and times of pathologic stress.

Areas of controversy: The classification is often confusing
and unable to simplify the understanding of the complexity.
Moreover, the multidimensional nature of hydrocephalus still
challenges newer attempts at classification into a satisfying
scheme.[4,6‑10]
Quo vadis:
The current definition of hydrocephalus does not satisfy the
complex and multidimensional nature of the pathology. It is,
at best, a pathophysiological definition.
Areas of controversy: The influence of various physiological
changes on CSF dynamics and the interaction of multiple CSF
flow system components[16] is controversial.
Quo vadis:
Mechanisms by which CSF circulation is produced,
absorbed, regulated, and influenced by age and pathology
are ongoing research. Future work is needed to understand
the intricacies of each and the active interactions between
the two systems.

A single classification to address these challenges and simplify “Normal” ICP in infancy and the selection of optimal valve pressure
this complex entity is elusive, and the utilitarian dimension of Uncertainty exists regarding normal ICP values during infancy,
such an approach is an additional challenge. and a widely cited reference defines normal ICP at 3.5 mmHg

S576 Neurology India | Volume 69 | Supplement 2 | November-December 2021

 Udayakumaran and Pattisapu: Controversies in hydrocephalus
in neonates and 5.8 mmHg in infants (6.4 mmHg in children
and 15.3 mmHg in adolescents and adult).[19] However, in other
reports on infants with craniosynostosis, mean ICP values of
less than 10 mmHg at rest are considered normal. Closely tied
to this issue is optimal initial valve pressure setting in newborns
and infants.[20]
Areas of agreement: It is uniformly agreed that infants have
low ICP and require low shunt valve settings.
Areas of controversy: Ideal pressure range in neonates and
infants remains poorly defined.
Quo vadis:
The ideal CSF pressures setting for infants will remain
questionable until the ICP issues are better understood.
Current thinking recommends using the lowest setting initially
and escalating as the perioperative risks of CSF leakage
subsides.
Nosological Controversies and Orphan Entities
a. Idiopathic Intracranial hypertension
b. Idiopathic Normal Pressure hydrocephalus
c. Ventriculomegaly of uncertain significance in children:
arrested and normal pressure hydrocephalus.
Idiopathic intracranial hypertension
Idiopathic intracranial hypertension (IIH) is a rare and poorly
understood condition, which appears to be strongly associated
with obesity. Therefore, correct diagnosis of papilledema and
early exclusion of other intracranial causes of raised ICP are
essential.
Areas of agreement: The definition has been defined with
clarity.
Although the exact pathogenesis remains unknown, there is
a strong association with obesity, typically centripetal and
androgen excess.[21]
ICP can be controlled with weight loss in most patients and
drugs that reduce CSF production.[22,23]
Areas of controversy: The etiology of IIH remains elusive
and largely theoretical. However, these theories drive many
treatment options or recommendations, including those related
to abnormal CSF physiology, such as increased production
and/or decreased absorption and pressure differentials within
the venous sinus system.[24]
Friedman et al.[25] included cases of IIH without papilledema
in a “probable” diagnostic category, and similar guidelines
were included in recently published consensus criteria.[26]
However, while IIH without papilledema is physiologically
possible, this diagnosis is controversial, given that unilateral
papilledema can occur. It hence should be made with caution
since it is more likely that an ICP measurement is falsely
elevated in a patient with a chronic primary headache
disorder than for a patient with intracranial hypertension not
to have papilledema.[27]
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S577
Quo vadis:
The nosology and pathophysiology of IIH remain uncertain.
Therefore, optimal treatment option varies from conservative
to ventriculoperitoneal shunt  (VPS), lumboperitoneal shunt
or optic nerve sheath fenestration, or venous sinus stenting,
depending on several factors.
Idiopathic normal pressure hydrocephalus (iNPH)
The entity and nosology of iNPH have recently received
renewed attention with significant scrutiny and academic
debate.[28] It is a clinical syndrome of older people (>60 years)[29,30]
caused by impaired CSF reabsorption and characterized
clinically by gait disturbance, cognitive dysfunction, and
urinary incontinence. However, the exact etiology of iNPH
is unknown.[31]
It may be managed conservatively or treated surgically
by inserting a ventriculoperitoneal or ventriculoatrial
shunt, lumboperitoneal shunt, or endoscopic
third ventriculostomy  (ETV). However, many
patients do not respond well to surgical treatment,
complication rates are high, and there is often a need for
further surgery. Therefore, as discussed elsewhere in this
symposium, diagnosis and timely interventions are under
discussion.
Areas of agreement:
1. It is a treatable form of dementia which is a reasonable
extent of patients responds to CSF diversion.
2. The causal relationship between aqueductal stroke velocity
and ventricular volume has been confirmed.[32]
3. The common consensus is that ventriculomegaly resulting
from CSF dynamics could initiate a vicious cycle of
neurological damages in iNPH. Pathophysiological
factors including hypoperfusion, glymphatic impairment,
metabolism disturbance, astrogliosis, neuroinflammation,
and blood–brain barrier disruption jointly cause white
matter and gray matter lesions and eventually lead to
various iNPH symptoms.
Areas of controversy:
1. Ostensibly, up to two‑thirds of patients with iNPH
can later evolve features of a definable entity (often
neurodegenerative), making the term “idiopathic”
somewhat controversial.[28]
2. A subgroup of these adults with long‑standing overt
ventriculomegaly may have congenital hydrocephalus
or aqueductal stenosis with enlarged lateral and third
ventricles.[33]
3. D e s p i t e o u r p r o g r e s s i n u n d e r s t a n d i n g i N P H ,
the exact pathophysiology and optimal management
of iNPH remain elusive and controversial. Thus, the
vital problem is identifying the subset of patients with
suspected iNPH who might benefit from shunting
procedures.[34]
4. Available guidelines differ in recommendations (i.e., age
cutoff or comorbidities), and none has received full
acceptance on a global level.[35,36]
Quo vadis:
There has been a paradigm shift in the last two decades,
recognizing that iNPH is not just a CSF disorder but a brain
 Udayakumaran and Pattisapu: Controversies in hydrocephalus
disorder expressing eloquently with ventriculomegaly.
Therefore, iNPH needs rethinking to determine the many
molecular and biological disruptions behind a disease that (for
too long) has remained “idiopathic”.[37]
Ventriculomegaly of uncertain significance in children:
Arrested and normal pressure hydrocephalus
Incidence of arrested hydrocephalus (AH) is
reportedly 10–15%,[6,38] but the condition may be gradually
progressive, with increasing incidence than previously
suggested.[39,40]
Areas of agreement: A syndrome in children and young
adults presenting with clinical findings similar to NPH
has been recognized.[41‑47] This is a form of communicating
hydrocephalus with normal intraventricular CSF pressure
resulting in progressive cerebral atrophy, ventricular dilation,
and impairment of developmental cognitive and gross motor
milestones.
Areas of controversy: The pediatric NPH/AH diagnosis
is backed by less substantial clinical evidence than adult
NPH. [46,48] However, if these children have harmless
ventriculomegaly or pressure‑compensated hydrocephalus,
it remains an essential controversy since detailed Magnetic
resonance imaging studies cannot distinguish between these
entities.[49]
Baseline CSF pressure and individual pressure
measurements may be in the normal range in
patients with chronic hydrocephalus. However,
continuous monitoring may reveal more dynamic pressure
alterations, such as “B waves,” or increased resistance
to CSF  (RCSF) outflow as documented in NPH  (>13
mm Hg/mL per minute). These findings have helped
differentiate NPH from both brain atrophy with normal
CSF circulation. Infusion studies in patients suffering
predominantly from brain atrophy typically demonstrate
low opening pressure, RCSF outflow, and low pulse
amplitude  (ICP  <12 mm  Hg, RCSF  <12 mm  Hg/mL per
minute, amplitude <2 mm Hg).[48]
However, it should be noted that the difficulties
of collecting continuous and reliable pressure
recordings for such purposes are limiting in the pediatric
setting.[48] Thus, data in this population lack to draw meaningful
conclusions.
In a study by Dias et al.,[50] ventriculomegaly in the absence
of signs and symptoms of raised ICP was associated in 62%
of cases to pathological ICP dynamics. Furthermore, in 80%
of pretreated cases, ETV closure or active shunt failure was
identified.[51] Thus, treating the children with abnormal ICP
dynamics resulted in an outcome at least as favorable as in the
group with normal ICP dynamics.
Quo vadis:
Asymptomatic ventriculomegaly (AH/NPH) in children
deserves further investigation. If associated with abnormal
ICP dynamics, it should be treated to provide normalized
intracranial physiology as a basis for the best possible long‑term
outcome.[50]
S578 Neurology India | Volume 69 | Supplement 2 | November-December 2021
Controversies in the management of hydrocephalus
a. ETV with choroid plexus cauterization
b. ETV in communicating hydrocephalus
c. ETV versus VP shunt: hydrodynamics and superior
outcome
d. The superiority of valves: fixed versus programmable.
ETV with choroid plexus cauterization
The addition of choroid plexus cauterization (CPC) to the ETV
procedure has improved the overall success rate.[52‑55] Recent
data suggest that a combined endoscopic third ventriculostomy
and choroid plexus coagulation (ETV‑CPC) has emerged as
a promising modality for the initial treatment of infantile
hydrocephalus.[55,56]
Areas of agreement: Combined ETV‑CPC is a promising
modality in infantile hydrocephalus.[55,56]
Areas of controversy: Beyond the early promise of the result
ETV‑CPC, the question remains whether the works can be
translated to the broader pediatric neurosurgery population
and whether the procedure has long‑term durability. Another
critical question is if ultimate cognitive outcomes are similar
to those of VP shunts and whether removing homeostatic and
trophic factors secreted by the choroid plexus has consequences
later in life.[57,58]
Quo vadis:
This is an open area of research with no clear answers; hence,
the treatment option needs to be taken cautiously, awaiting
further long‑term studies.
ETV in communicating hydrocephalus
Conceptually, ETV will only be effective in hydrocephalus
with intraventricular obstruction to CSF outflow. The
modified bulk flow theory  (suggesting all hydrocephalus
has some obstruction) can explain the effectiveness
of ETV in treating some types of communicating
hydrocephalus, such as posttraumatic, posthemorrhagic,
postmeningitis hydrocephalus,[59] and iNPH.[60] However,
this approach is not widely accepted and subject to
controversy.
Lately, CSF is thought to be absorbed via capillary
vessels.[12] Particularly, in children less than 2 years old, most
CSF absorption depends on capillary vessels of ventricular
ependyma because of the immaturity of arachnoid villi. [9]
An increase of intraventricular pulsatile pressure decreases
CSF absorption via capillary vessels.[61,62] As the absorption
via capillary vessels decreases, CSF gradually accumulates,
resulting in a decreased intracranial venous volume that
buffers pulsatile pressure. Furthermore, it decreases the
CSF absorption via capillary vessels and accumulates CSF,
which falls in a vicious cycle.[63] ETV terminates this cycle by
making a stoma connecting the cisternal space through which
a pulsatile pressure can be buffered, and CPC attenuates
pulsatile pressure originating from the choroid plexus. This
theory can be applied to the case of noncommunicating
hydrocephalus in which a pressure gradient exists between
intra‑  and extraventricular space. However, it is unknown
whether pulsatile pressure between the ventricle and cisternal
 Udayakumaran and Pattisapu: Controversies in hydrocephalus
space is constant. Therefore, there may be a pressure gradient
even in the case of communicating hydrocephalus. In such a
case, ETV with/without CPC can be effective. In case of failure,
ETV and CPC may not have achieved a sufficient reduction
of pulsatile pressure, or the CSF absorptive function in the
intraventricular glymphatic system may have been lost by
infection or hemorrhage.
Areas of agreement: Literature review suggests ETV might
have a role in specific selected clinical scenarios of truly
communicating hydrocephalus (limited data exist, however).
Areas of controversy: The success rate after ETV focusing on
pure communicating hydrocephalus is still unknown. Bulk
flow theory cannot explain the improvement of communicating
hydrocephalus after ETV alone or ETV with CPC.
Quo vadis:
ETV might be useful in some instances, and the evidence
of increased failure risk in the treatment of communicating
hydrocephalus when using ETV compared to VPS remains
weak.[64] However, the selection of appropriate cases will
require further understanding of the pathophysiology of
hydrocephalus.
ETV versus VP shunt: Hydrodynamics and superior outcome
The optimum permanent treatment for hydrocephalus is
controversial, and debate remains regarding indications for
the shunts versus ETV, especially in very young infants.[65‑67]
Area of agreement: Shunting is generally associated with a
smaller ventricular size than post‑ETV.[68]
Areas of controversy: Whether a difference in ventricles and
cortical mantle thickness has functional or developmental,
implications remains controversial, mainly because of limited
existing literature.[69] Additionally, interesting discussions
regarding shunt and ETV’’s efficiency  (concerning CSF
hydrodynamics) are, for instance, ventricular fluid is
drained by the shunt and ETV facilitates subarachnoid fluid
removal.[70]
Quo vadis:
Available literature supports ETV as a valid and effective
treatment for hydrocephalus. However, insufficient evidence
is available to justify the shunting option over this procedure
toward a better neurocognitive outcome.[71‑75]
Superiority of valves: Fixed versus programmable
Although the reports contradict, some data suggest that
programmable valves may reduce failure/revision rates
compared with fixed pressure valves, [76,77] There is little
to no difference in outcomes with standard shunt valves
compared to antisiphon or self‑adjusting CSF flow‑regulating
valves  (evidence is unfortunately based on low or very
low quality of certainty).[78‑80] Similarly, differential valves
and programmable pressure valves may be associated
with similar outcomes compared with nonprogrammable
valves.[81,82]
Areas of agreement: Programmable valve may reduce the
revision rate and over‑or under‑drainage complication
Neurology India | Volume 69 | Supplement 2 | November-December 2021 S579
rate. These valves are not associated with decreased overall
complication rates in patients with hydrocephalus.[83]
Gravity assisted valves are designed to minimize overdrainage,
especially the problem of siphoning and under drainage.
Numerous clinical trials have supported the conclusion that
gravitational valves may reduce by half the rate of occurrence
of overdrainage to 3–5%,[84‑86] while the risk of under drainage
is increased.[87]
Areas of controversy: Whether the use of programmable valves
affects the outcome is controversial.
Quo vadis:
Due to the complexity of the hydrocephalus condition, lifelong
follow‑up care for patients with VPS is critical.
Standard/nonprogrammable valves and programmable
pressure valves offer similar outcomes, although the quality
of evidence is of low certainty.[81] More data from ongoing
prospective studies regarding the safety and efficacy of
adjustable gravitational valves are still pending.[88]
Controversies in the Outcome of Treated
Hydrocephalus: Brain Mantle Thickness, Ventricular
Size, and Outcome
Brain volume correlates with a cognitive outcome better than CSF
volume, suggesting promoting brain growth as the more critical
measure of truly successful treatment.[34,89] In addition, some
animal studies have shown that compensated hydrocephalus
has increased the accumulation of phosphorylated tau protein
in the cerebral cortex. Some suggest that this may be a possible
mechanism of later cognitive decline.[90]
Areas of agreement: The literature is sparse regarding cognitive
changes related to ventricular size. More baseline data are
needed before commenting that smaller ventricles or less ICP
are beneficial in this population.[91‑94] In addition, persistent
ventriculomegaly, especially after treatment with ETV, is
common even after symptom alleviation.
Areas of controversy: It is not clear whether persistent
ventriculomegaly can in itself cause subtle white matter injury
or impair cognitive outcome.
Quo vadis:
Ventricular size and cortical mantle indeed mark the successful
diversion of excess CSF. However, the extent of change that
is possible and necessary to determine the cognitive outcome
is a gray area.
Limitations
We have not aimed for a comprehensive summary of all
published studies on this vast topic but sought to highlight
controversial or poorly understood areas. Further discussion
regarding these targeted issues and are foundations for future
research endeavors. Moreover, in science, controversy is
subjective and time related  –  often, a fine line differentiates
it from gaps of knowledge. Understanding such dilemmas
provide research objectives or, more precisely, a concept to
unify these discussions.
 Udayakumaran and Pattisapu: Controversies in hydrocephalus
Conclusions
A complex entity such as hydrocephalus is poorly understood
with many diagnostic and treatment challenges. Until we
understand this condition fully, controversy will exist, which
will hopefully drive the scientific rigor to newer heights. This
review is a simple compilation of “sparks” for future endeavors
on the challenging theme of hydrocephalus.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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 NI Feature: The First Impression

The First Impression

The photograph shows a man in pain with a child with Dr Mahendra Singh Chouhan
Hydrocephalus. The pain of the father is clear for obvious reasons.
The photo has a rustic feel as the problem of Hydrocephalus M.Ch (AIIMS Delhi),
looms large on us for ages. As Neurosurgeons, all of us have Senior consultant Brain and Spine diseases
Email: mscneuro@gmail.com`
seen the misery of parents who have Hydrocephalus with
repeated shunt issues, the way they get affected emotionally This is an open access journal, and articles are distributed under the terms of the Creative
and financially. Commons Attribution‑NonCommercial‑ShareAlike 4.0 License, which allows others to remix,
tweak, and build upon the work non‑commercially, as long as appropriate credit is given and
the new creations are licensed under the identical terms.
Hydrocephalus always behaves in its own elusive ways,
sometimes patients with hydrocephalus get full relief and at
other times they keep coming back with repeated failures. Access this article online
Even the most experienced surgeons would have experienced Quick Response Code
Website:
frustrations with this pathology. It's no doubt an enigma, where www.neurologyindia.com
we still need to understand a lot.
DOI:
10.4103/0028-3886.332523
The author in this artistic rendition has tried to depict all
these distresses. However, this picture also depicts that the PMID:
child with hydrocephalus is holding a ventriculoscope in his ***
hand symbolizing the emerging new concepts of endoscopy
as opposed to the shunt held in the hand of the old man
personifying the 'old' technique.
How to cite this article: Chouhan MS. The First Impression. Neurol
India 2021;69:S583.
The picture oozes hope in a way that the child is consoling the
Submitted: 02‑Nov‑2021  
old man with a smile to try a new technique and his smile and
Accepted: 02‑Nov‑2021   Published: 11-Dec-2021
touch is the symbolism of hope.
© 2021 Neurology India, Neurological Society of India | Published by Wolters Kluwer - Medknow S583